PEX11G (peroxisomal membrane protein 11C, also known as PEX11-gamma) is the third and least characterized member of the human PEX11 family of peroxisomal membrane proteins (PMID:12559946). It is a multi-pass integral membrane protein of the peroxisome that promotes membrane protrusion and elongation on the peroxisomal surface, contributing to peroxisome proliferation and maintenance (PMID:20826455). PEX11G forms homodimers and heterodimers with PEX11A and PEX11B, and interacts with the fission adaptors FIS1 and MFF, linking membrane elongation to the fission machinery (PMID:20826455, PMID:22595523). The protein contains a functional amphipathic helix that promotes membrane bending/elongation (PMID:22595523). Unlike the inducible PEX11A, PEX11G is constitutively expressed and shows tissue-enhanced expression in liver and testis (PMID:12559946). Overexpression of PEX11G can partially rescue peroxisome morphology defects in PEX11B-deficient patient fibroblasts under stress conditions, suggesting functional compensation potential among isoforms (DOI:10.3390/cells11121922).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005778
peroxisomal membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: PEX11G is well-established as a peroxisomal membrane protein. IBA annotation via phylogenetic inference is consistent with experimental data from multiple studies showing localization to the peroxisomal membrane (PMID:12559946, PMID:20826455, PMID:12417726). UniProt records this as a multi-pass membrane protein of the peroxisome membrane with evidence from three independent publications. Koch and Brocard (PMID:22595523) further confirmed PEX11G as a true integral peroxisomal membrane protein not extractable by sodium carbonate.
Reason: Peroxisomal membrane localization is a core property of PEX11G, confirmed by immunofluorescence colocalization with PTS1-tagged peroxisomal markers (PMID:12559946), carbonate extraction experiments (PMID:22595523), and additional studies (PMID:20826455, PMID:12417726). The IBA annotation is phylogenetically sound and experimentally validated.
Supporting Evidence:
PMID:12559946
Pex11pgamma was found to be a peroxisomal membrane protein, as assessed by colocalization with peroxisome targeting signal type 1 (PTS1)-proteins, in epitope-tagged Pex11pgamma-expressing Chinese hamster ovary cells.
PMID:20826455
Dynamic changes of membrane structure are intrinsic to organelle morphogenesis and homeostasis. Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs)
file:human/PEX11G/PEX11G-deep-research-falcon.md
PEX11G is clearly a peroxisomal integral membrane protein with membrane-shaping motifs, and it can drive elongation when overexpressed
|
|
GO:0016559
peroxisome fission
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA annotation for peroxisome fission. PEX11 family members are established as membrane elongation factors that coordinate peroxisome proliferation (PMID:20826455). The Koch et al. 2010 paper demonstrates that PEX11 proteins induce formation of juxtaposed elongated peroxisomes (JEPs) as intermediates in the peroxisome fission process, and that FIS1 is the limiting factor for progression to fission. PEX11G is more precisely a membrane elongation factor that acts upstream of the actual fission event, but peroxisome fission is a reasonable annotation for the overall process it participates in.
Reason: While PEX11G is more directly involved in the membrane elongation step rather than the fission step per se, the overall biological process of peroxisome fission encompasses the elongation-to-division pathway. The IBA annotation appropriately captures PEX11G involvement in this process.
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:0005778
peroxisomal membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: IEA annotation for peroxisomal membrane localization via combined automated methods. This is consistent with the experimentally validated IDA and IBA annotations for the same term. Redundant but not incorrect.
Reason: Automated annotation is consistent with all experimental evidence. Peroxisomal membrane localization is the core cellular component for PEX11G.
|
|
GO:0016559
peroxisome fission
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA annotation for peroxisome fission via InterPro-to-GO mapping. The PEX11 InterPro domain (IPR008733) maps to this process. This is consistent with the IBA and IDA annotations for the same term and supported by the Koch et al. 2010 experimental data.
Reason: The InterPro-based annotation is correct. PEX11G belongs to the PEX11 family (IPR008733, Pfam PF05648) which is functionally characterized as involved in peroxisome fission/proliferation.
|
|
GO:0005515
protein binding
|
IPI
PMID:32296183 A reference map of the human binary protein interactome. |
REMOVE |
Summary: Protein binding annotation from the HuRI high-throughput yeast two-hybrid interactome study (Luck et al. 2020, PMID:32296183). The UniProt record lists interactions with AQP6, ERGIC3, KCNJ6, TMEM14B, and TMEM86B from IntAct with 3 experiments each. These are all membrane proteins but none have obvious biological connection to peroxisome biology. These interactions from a high-throughput screen likely represent non-physiological membrane protein interactions in the Y2H system.
Reason: Generic protein binding is uninformative. The interactions reported from the HuRI high-throughput Y2H screen (PMID:32296183) are with proteins that have no known connection to peroxisome biology (AQP6 is an aquaporin, ERGIC3 is an ER-Golgi protein, KCNJ6 is a potassium channel). These are likely artifacts of the high-throughput assay. The biologically relevant interactions of PEX11G (with PEX11A, PEX11B, and FIS1) are documented in PMID:20826455 but are not captured by this annotation.
Supporting Evidence:
PMID:32296183
HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins
|
|
GO:0005778
peroxisomal membrane
|
IDA
PMID:12559946 cDNA cloning and characterization of the third isoform of hu... |
ACCEPT |
Summary: Direct experimental evidence for peroxisomal membrane localization from the original PEX11G cloning and characterization paper (Tanaka et al. 2003). The authors showed colocalization of epitope-tagged PEX11G with PTS1-proteins in CHO cells and demonstrated a two-transmembrane-segment topology with both N- and C-termini facing the cytosol.
Reason: This is the primary experimental evidence for PEX11G peroxisomal membrane localization. Direct immunofluorescence and topology studies provide strong evidence for this core annotation.
Supporting Evidence:
PMID:12559946
Pex11pgamma was found to be a peroxisomal membrane protein, as assessed by colocalization with peroxisome targeting signal type 1 (PTS1)-proteins, in epitope-tagged Pex11pgamma-expressing Chinese hamster ovary cells. Pex11pgamma exposes both of the N- and C-terminal parts to the cytosol.
|
|
GO:0005515
protein binding
|
IPI
PMID:20826455 PEX11 family members are membrane elongation factors that co... |
MODIFY |
Summary: Protein binding annotation from Koch et al. 2010 which demonstrated homo- and heterodimerization of PEX11 family members and interaction with the fission factor FIS1. While the interactions are biologically meaningful, the generic term 'protein binding' fails to capture the specific nature of these interactions. PEX11G forms homodimers and heterodimers with PEX11A and PEX11B, and interacts with FIS1 to coordinate peroxisome elongation and fission.
Reason: The term 'protein binding' (GO:0005515) is too generic and uninformative. The biologically relevant interactions are specific: homodimerization, heterodimerization with PEX11A/PEX11B, and interaction with FIS1. These should be captured with more specific molecular function terms.
Proposed replacements:
protein homodimerization activity
protein heterodimerization activity
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: Annotation to the broader term 'peroxisome' (GO:0005777) based on Koch et al. 2010. PEX11G is more specifically localized to the peroxisomal membrane (GO:0005778), which is a child term of peroxisome. Since the more specific term is already annotated with both IDA and IBA evidence, this broader annotation is redundant but not incorrect.
Reason: While redundant with the more specific GO:0005778 (peroxisomal membrane) annotations, this is not incorrect. The peroxisome annotation encompasses the membrane localization. Some annotation pipelines retain both levels.
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)
|
|
GO:0016559
peroxisome fission
|
IDA
PMID:20826455 PEX11 family members are membrane elongation factors that co... |
ACCEPT |
Summary: Direct experimental evidence for involvement in peroxisome fission from Koch et al. 2010. The study demonstrated that ectopic expression of PEX11 family members (including PEX11G) leads to formation of juxtaposed elongated peroxisomes (JEPs), which are intermediates in the peroxisome fission process. Excess FIS1 fragments these JEPs into normal round peroxisomes, demonstrating that PEX11-induced elongation is an intermediate step in fission. This is a core function of PEX11G.
Reason: Koch et al. 2010 provides direct experimental evidence that PEX11G promotes the membrane elongation step of peroxisome fission. While PEX11G acts specifically at the elongation stage rather than the scission step, the overall process annotation to peroxisome fission is appropriate as the elongation is an integral part of the fission pathway.
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. Hence, we propose a model for a conserved role of PEX11 proteins in peroxisome maintenance through peroxisome polarization, membrane elongation and segregation.
|
|
GO:0032991
protein-containing complex
|
IDA
PMID:20826455 PEX11 family members are membrane elongation factors that co... |
MARK AS OVER ANNOTATED |
Summary: Annotation to the generic 'protein-containing complex' term based on Koch et al. 2010, which demonstrated that PEX11G forms homodimers and heterodimers with PEX11A and PEX11B. While the formation of these complexes is experimentally supported, the term is extremely generic and uninformative. A more specific complex term would be preferable but none exists in GO for PEX11 complexes.
Reason: The term 'protein-containing complex' (GO:0032991) is too broad to be informative. While PEX11G does form homo- and heterodimeric complexes, annotating to this very generic CC term adds little value. The specific interaction partners are better captured through molecular function annotations (e.g., homodimerization activity).
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: Annotation for regulation of peroxisome size based on Koch et al. 2010. PEX11G promotes membrane elongation, which changes peroxisome morphology from round to elongated tubular structures (JEPs). This does affect peroxisome size/shape as an intermediate in the proliferation process. The term definition is "any process that modulates the volume of a peroxisome," which is consistent with the membrane elongation activity of PEX11G.
Reason: PEX11G-induced membrane elongation directly modulates peroxisome size and shape, converting round peroxisomes into elongated tubular structures. This is a core function of PEX11G and the term accurately captures this activity.
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:0042803
protein homodimerization activity
|
IDA
PMID:20826455 PEX11 family members are membrane elongation factors that co... |
NEW |
Summary: New annotation proposed to replace the generic 'protein binding' annotation from PMID:20826455. Koch et al. 2010 established that PEX11G forms homodimers, which is part of its functional mechanism in membrane elongation.
Reason: Koch et al. 2010 demonstrated homodimerization of PEX11G as part of its functional characterization. This is a more informative molecular function term than generic protein binding.
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:0180020
membrane bending activity
|
IDA
PMID:22595523 PEX11 proteins attract Mff and human Fis1 to coordinate pero... |
NEW |
Summary: New annotation proposed for the primary PEX11G molecular function. PEX11G uses membrane-anchored domains and an amphipathic region to dock into the peroxisomal membrane and regulate membrane elongation/protrusion, which is better captured as membrane bending activity than by dimerization alone.
Reason: The core molecular activity supported by the topology and mutagenesis work is membrane remodeling/bending during peroxisome elongation. Homo- and heterodimerization are mechanistic supporting interactions, but membrane bending is the most specific GO molecular function for the primary activity.
Supporting Evidence:
PMID:22595523
we establish that the PEX11gamma sequence includes two membrane-anchored domains, which dock an amphipathic region onto the peroxisomal membrane thereby regulating its elongation
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The literature retrieved explicitly equates human PEX11G with PEX11γ/PEX11C/PEX11c, a member of the PEX11 peroxin family and a peroxisomal integral membrane protein involved in peroxisome membrane dynamics (elongation and division coordination). This matches the user-provided UniProt identity for Q96HA9 (Peroxisomal membrane protein 11C; Peroxin-11C; Protein PEX11 homolog gamma). (koch2012pex11proteinsattract pages 2-3, koch2012pex11proteinsattract pages 1-2)
Mammalian peroxisomes can proliferate through membrane growth/elongation followed by constriction and fission, a process coordinated by the PEX11 family together with shared fission machinery components also used by mitochondria (adaptors such as MFF and FIS1 and the fission GTPase DRP1). This framework is emphasized in expert syntheses of peroxisome dynamics disorders and peroxisome biology. (carmichael2022fissionimpossible(?)—new pages 5-6, carmichael2022fissionimpossible(?)—new pages 2-5)
PEX11 proteins are generally positioned as membrane-shaping/remodeling factors that support elongation and help organize recruitment of the membrane scission machinery; they are not enzymes with a catalytic active site in these sources, but rather structural/membrane remodeling proteins that act via membrane insertion, amphipathic helices, oligomerization, and protein–protein interactions. (koch2012pex11proteinsattract pages 1-2, koch2012pex11proteinsattract pages 6-7)
Koch & Brocard (2012; Journal of Cell Science; Aug 2012; https://doi.org/10.1242/jcs.102178) experimentally established that PEX11γ/PEX11c (PEX11G) is a true integral peroxisomal membrane protein: it is not extractable by sodium carbonate and is detected in the membrane fraction. (koch2012pex11proteinsattract pages 2-3)
Koch & Brocard mapped PEX11γ topology and motifs, reporting:
- The N-terminus of PEX11γ lies on the cytosolic face of the peroxisomal membrane. (koch2012pex11proteinsattract pages 2-3)
- Both N- and C-termini are cytosolic in their topology model for PEX11γ/PEX11c. (koch2012pex11proteinsattract pages 10-11)
- The protein contains two membrane-buried hydrophobic regions and a functional amphipathic helix that is proposed to dock on the membrane outer leaflet to promote bending/elongation; mutating the amphipathic helix (A182P) reduces elongation. (koch2012pex11proteinsattract pages 6-7, koch2012pex11proteinsattract pages 7-8)
A schematic depiction of PEX11γ topology and an amphipathic helix model are available from this paper’s figure panels. (koch2012pex11proteinsattract media 14ffab39, koch2012pex11proteinsattract media 9c614795)
In cell-based assays, overexpression of PEX11γ/PEX11c drives peroxisome elongation and the formation of juxtaposed elongated peroxisomes (JEPs), supporting the concept that PEX11 proteins act as membrane elongation factors in mammals. (koch2012pex11proteinsattract pages 1-2, koch2012pex11proteinsattract pages 7-8)
Koch & Brocard report interaction/association evidence that places PEX11γ in the peroxisome division network:
- PEX11γ co-precipitates with Mff and co-precipitates/interacts with hFis1. (koch2012pex11proteinsattract pages 7-8, koch2012pex11proteinsattract pages 10-11)
- PEX11γ associates with PEX11β (hetero-oligomerization) and shows altered association patterns in mutants affecting elongation, linking topology/oligomerization to recruitment/coordination of division factors. (koch2012pex11proteinsattract pages 1-2, koch2012pex11proteinsattract pages 10-11)
A model diagram from Koch & Brocard summarizes a multi-step sequence where PEX11 proteins promote membrane protrusion/elongation and then recruit/adapt fission components (Mff/hFis1/DRP1) for scission. (koch2012pex11proteinsattract media 4d08d3ba)
A 2024 review (“The peroxisome: an update on mysteries 3.0”; Histochemistry and Cell Biology; Jan 2024; https://doi.org/10.1007/s00418-023-02259-5) provides a recent field-level update on peroxisome functions, biogenesis, and membrane dynamics. While PEX11 isoforms are part of the membrane dynamics framework, within the retrieved evidence here the most explicit and detailed PEX11γ statements are contained in the 2022 disorder-focused review and in primary mechanistic work (below). (carmichael2022fissionimpossible(?)—new pages 5-6, carmichael2022fissionimpossible(?)—new pages 2-5)
A specialist review on peroxisome dynamics disorders (Cells; Jun 2022; https://doi.org/10.3390/cells11121922) emphasizes that PEX11β is the best-characterized isoform in mammals, and that the roles of PEX11α and PEX11γ remain less clear—highlighting a major open question that persists into the current understanding. (carmichael2022fissionimpossible(?)—new pages 5-6, carmichael2022fissionimpossible(?)—new pages 2-5)
Schrader et al. (Journal of Cell Science; 2022; https://doi.org/10.1242/jcs.259924) compared isoforms and observed that in PEX19-deficient fibroblasts (lacking peroxisomes), PEX11α and PEX11γ did not localize to mitochondria, whereas PEX11β did and could induce mitochondrial division upon targeting/overexpression. This supports functional specialization among isoforms and indicates PEX11γ does not share the same mislocalization-driven mitochondrial phenotypes as PEX11β. (schrader2022pex11βandfis1 pages 8-10)
In the retrieved expert review evidence, no human patients with PEX11G (PEX11γ) mutations have been reported to date, in contrast to PEX11B where patient cohorts exist. (carmichael2022fissionimpossible(?)—new pages 15-16)
Carmichael et al. summarize that in PEX11β-deficient patient fibroblasts, PEX11γ mRNA and protein decrease substantially at elevated temperature (40 °C), and that overexpression of PEX11γ (but not PEX11α) can partially rescue catalase import defects and abnormal peroxisome morphology under this stress condition (though less effectively than PEX11β re-expression). This positions PEX11γ as a potential compensatory factor under certain conditions. (carmichael2022fissionimpossible(?)—new pages 15-16)
Beltran et al. (Cell Host & Microbe; Oct 2018; https://doi.org/10.1016/j.chom.2018.09.002) built a targeted PRM proteomics assay of the peroxisome proteome during HCMV infection. They report:
- Evidence for 83 human peroxisomal proteins from curated datasets; 60 could be quantified by MS in primary human fibroblasts, while 23 were tissue-specific/low-abundance—explicitly including PEX11A and PEX11G as examples. (beltran2018infectioninducedperoxisomebiogenesis pages 3-4)
- During infection, 52/60 quantified peroxisomal proteins showed statistically significant association with infection time/condition. (beltran2018infectioninducedperoxisomebiogenesis pages 3-4)
This dataset is used as a real-world implementation of peroxisome biology measurements in infection and can guide expectations for detectability of PEX11G protein in specific cell types (e.g., low abundance in fibroblasts). (beltran2018infectioninducedperoxisomebiogenesis pages 3-4)
In the same study, HCMV infection increased peroxisome abundance with clear quantitative readouts: peroxisome numbers per cell increased 3.6-fold at 96 hours post-infection, and peroxisome concentration increased 2.6-fold at 96 hpi. (beltran2018infectioninducedperoxisomebiogenesis pages 5-6)
Beltran et al. report that peroxisomes are important for efficient HCMV replication: cells lacking peroxisomes (PEX3/PEX19 knockouts) show defective virus replication, while a peroxisome fission defect background (PEX11B knockout; enlarged/elongated peroxisomes) did not inhibit—and even increased—virus production, indicating that modulating peroxisome abundance/dynamics can affect infection outcomes. (beltran2018infectioninducedperoxisomebiogenesis pages 5-6)
Although this evidence focuses on PEX11B rather than PEX11G, it demonstrates how PEX11-family-mediated membrane dynamics can be leveraged in real cellular contexts and motivates translational interest in peroxisome remodeling pathways. (beltran2018infectioninducedperoxisomebiogenesis pages 5-6)
| Aspect | Key findings | Evidence type | Primary sources |
|---|---|---|---|
| Identity/nomenclature | Human PEX11G is also referred to as PEX11γ/PEX11c; a peroxin-11 family member and peroxisomal membrane protein | Primary mechanistic study; peroxin-11 family context | Koch & Brocard 2012, J Cell Sci, 10.1242/jcs.102178 (koch2012pex11proteinsattract pages 2-3, koch2012pex11proteinsattract pages 1-2) |
| Localization | Integral peroxisomal membrane protein; N- and C-termini face cytosol; co-localizes with PEX14/peroxisomes | Biochemical carbonate extraction, mPEG cysteine mapping, imaging | Koch & Brocard 2012, J Cell Sci, 10.1242/jcs.102178 (koch2012pex11proteinsattract pages 10-11, koch2012pex11proteinsattract pages 7-8) |
| Topology/domains | Two membrane-buried helices position an amphipathic helix on the cytosolic face; amphipathic helix integrity (A182P) modulates elongation phenotype | Topology mapping; mutational analysis | Koch & Brocard 2012, J Cell Sci, 10.1242/jcs.102178 (koch2012pex11proteinsattract pages 6-7, koch2012pex11proteinsattract pages 7-8) |
| Functional role | Promotes peroxisomal membrane elongation (juxtaposed elongated peroxisomes, JEPs) and coordinates division with fission machinery | Overexpression morphology; pathway modeling | Koch & Brocard 2012, J Cell Sci, 10.1242/jcs.102178 (koch2012pex11proteinsattract pages 7-8, koch2012pex11proteinsattract pages 11-12) |
| Interactions | Interacts with Mff and hFis1; forms homo-/hetero-oligomers with PEX11β; positions fission adaptors at elongation sites | Co-IP/biochemistry; imaging colocalization; model figure | Koch & Brocard 2012, J Cell Sci, 10.1242/jcs.102178 (koch2012pex11proteinsattract pages 7-8, koch2012pex11proteinsattract pages 10-11, koch2012pex11proteinsattract media 4d08d3ba) |
| Phenotypes & disease evidence | No human patients with PEX11G mutations reported; in PEX11B-deficient fibroblasts, PEX11γ expression drops at 40°C and PEX11γ overexpression partially rescues catalase import and morphology under heat stress | Expert review synthesis; patient cell studies summarized | Carmichael et al. 2022, Cells, 10.3390/cells11121922 (carmichael2022fissionimpossible(?)—new pages 15-16) |
| Recent developments & open questions | Roles of PEX11α/PEX11γ remain less clear vs PEX11β; PEX11β-specific sequence features (e.g., glycine-rich loop) are absent in PEX11γ; need to define γ-specific mechanisms/regulation | Review synthesis; comparative isoform analysis | Schrader et al. 2022, J Cell Sci, 10.1242/jcs.259924 (schrader2022pex11βandfis1 pages 3-5, schrader2022pex11βandfis1 pages 8-10); Carmichael et al. 2022, Cells, 10.3390/cells11121922 (carmichael2022fissionimpossible(?)—new pages 2-5) |
| Applications & implementations | Viral infection leverages peroxisome biogenesis: PEX11B KO (elongated peroxisomes) can enhance HCMV production; targeted PRM quantified peroxisome proteome (PEX11G low-abundance in HFs); PKC signaling promotes peroxisome formation via a PEX11b-dependent pathway | Virology/functional genomics; targeted proteomics (PRM); signaling study | Beltran et al. 2018, Cell Host Microbe, 10.1016/j.chom.2018.09.002 (beltran2018infectioninducedperoxisomebiogenesis pages 5-6, beltran2018infectioninducedperoxisomebiogenesis pages 3-4); Borisyuk et al. 2025, J Cell Biol, 10.1083/jcb.202505040 (borisyuk2025proteinkinasec pages 3-4) |
| Quantitative data points | Peroxisome proteins: 83 curated; 60 quantified by PRM in HFs; 52/60 significantly infection-associated; growth+fission events ~10–20× de novo; peroxisome number ↑3.6× at 96 hpi (HCMV); PEX11A/PEX11G noted as low-abundance in HFs (not quantified) | Proteomics (PRM); live-cell inference; morphometrics | Beltran et al. 2018, Cell Host Microbe, 10.1016/j.chom.2018.09.002 (beltran2018infectioninducedperoxisomebiogenesis pages 3-4, beltran2018infectioninducedperoxisomebiogenesis pages 6-8, beltran2018infectioninducedperoxisomebiogenesis pages 5-6) |
Table: Concise, evidence-based summary of human PEX11G (PEX11γ/PEX11C) identity, localization, topology, roles, interactions, and clinical context, with recent developments and quantitative datasets. Citations link to primary experiments, reviews, and quantitative studies relevant to PEX11 family biology.
Koch & Brocard’s figures include: (i) a schematic model of PEX11γ’s role in elongation/fission and recruitment of Mff/Fis1/DRP1 and (ii) PEX11γ topology and amphipathic helix diagrams. (koch2012pex11proteinsattract media 4d08d3ba, koch2012pex11proteinsattract media 14ffab39, koch2012pex11proteinsattract media 9c614795)
References
(koch2012pex11proteinsattract pages 2-3): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract pages 1-2): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(carmichael2022fissionimpossible(?)—new pages 5-6): Ruth E. Carmichael, Markus Islinger, and Michael Schrader. Fission impossible (?)—new insights into disorders of peroxisome dynamics. Cells, 11:1922, Jun 2022. URL: https://doi.org/10.3390/cells11121922, doi:10.3390/cells11121922. This article has 23 citations.
(carmichael2022fissionimpossible(?)—new pages 2-5): Ruth E. Carmichael, Markus Islinger, and Michael Schrader. Fission impossible (?)—new insights into disorders of peroxisome dynamics. Cells, 11:1922, Jun 2022. URL: https://doi.org/10.3390/cells11121922, doi:10.3390/cells11121922. This article has 23 citations.
(koch2012pex11proteinsattract pages 6-7): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract pages 10-11): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract pages 7-8): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract media 14ffab39): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract media 9c614795): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(koch2012pex11proteinsattract media 4d08d3ba): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(schrader2022pex11βandfis1 pages 8-10): Tina A. Schrader, Ruth E. Carmichael, Markus Islinger, Joseph L. Costello, Christian Hacker, Nina A. Bonekamp, Jochen H. Weishaupt, Peter M. Andersen, and Michael Schrader. Pex11β and fis1 cooperate in peroxisome division independently of mitochondrial fission factor. Journal of Cell Science, Jul 2022. URL: https://doi.org/10.1242/jcs.259924, doi:10.1242/jcs.259924. This article has 33 citations and is from a domain leading peer-reviewed journal.
(carmichael2022fissionimpossible(?)—new pages 15-16): Ruth E. Carmichael, Markus Islinger, and Michael Schrader. Fission impossible (?)—new insights into disorders of peroxisome dynamics. Cells, 11:1922, Jun 2022. URL: https://doi.org/10.3390/cells11121922, doi:10.3390/cells11121922. This article has 23 citations.
(beltran2018infectioninducedperoxisomebiogenesis pages 3-4): Pierre M. Jean Beltran, Katelyn C. Cook, Yutaka Hashimoto, Cyril Galitzine, Laura A. Murray, Olga Vitek, and Ileana M. Cristea. Infection-induced peroxisome biogenesis is a metabolic strategy for herpesvirus replication. Cell host & microbe, 24 4:526-541.e7, Oct 2018. URL: https://doi.org/10.1016/j.chom.2018.09.002, doi:10.1016/j.chom.2018.09.002. This article has 100 citations and is from a highest quality peer-reviewed journal.
(beltran2018infectioninducedperoxisomebiogenesis pages 5-6): Pierre M. Jean Beltran, Katelyn C. Cook, Yutaka Hashimoto, Cyril Galitzine, Laura A. Murray, Olga Vitek, and Ileana M. Cristea. Infection-induced peroxisome biogenesis is a metabolic strategy for herpesvirus replication. Cell host & microbe, 24 4:526-541.e7, Oct 2018. URL: https://doi.org/10.1016/j.chom.2018.09.002, doi:10.1016/j.chom.2018.09.002. This article has 100 citations and is from a highest quality peer-reviewed journal.
(beltran2018infectioninducedperoxisomebiogenesis pages 6-8): Pierre M. Jean Beltran, Katelyn C. Cook, Yutaka Hashimoto, Cyril Galitzine, Laura A. Murray, Olga Vitek, and Ileana M. Cristea. Infection-induced peroxisome biogenesis is a metabolic strategy for herpesvirus replication. Cell host & microbe, 24 4:526-541.e7, Oct 2018. URL: https://doi.org/10.1016/j.chom.2018.09.002, doi:10.1016/j.chom.2018.09.002. This article has 100 citations and is from a highest quality peer-reviewed journal.
(koch2012pex11proteinsattract pages 11-12): Johannes Koch and Cécile Brocard. Pex11 proteins attract mff and human fis1 to coordinate peroxisomal fission. Journal of Cell Science, 125:3813-3826, Aug 2012. URL: https://doi.org/10.1242/jcs.102178, doi:10.1242/jcs.102178. This article has 128 citations and is from a domain leading peer-reviewed journal.
(schrader2022pex11βandfis1 pages 3-5): Tina A. Schrader, Ruth E. Carmichael, Markus Islinger, Joseph L. Costello, Christian Hacker, Nina A. Bonekamp, Jochen H. Weishaupt, Peter M. Andersen, and Michael Schrader. Pex11β and fis1 cooperate in peroxisome division independently of mitochondrial fission factor. Journal of Cell Science, Jul 2022. URL: https://doi.org/10.1242/jcs.259924, doi:10.1242/jcs.259924. This article has 33 citations and is from a domain leading peer-reviewed journal.
(borisyuk2025proteinkinasec pages 3-4): Anya Borisyuk, Charlotte Howman, Sundararaghavan Pattabiraman, Daniel Kaganovich, and Triana Amen. Protein kinase c promotes peroxisome biogenesis and peroxisome–endoplasmic reticulum interaction. The Journal of Cell Biology, Jul 2025. URL: https://doi.org/10.1083/jcb.202505040, doi:10.1083/jcb.202505040. This article has 5 citations.
id: Q96HA9
gene_symbol: PEX11G
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
PEX11G (peroxisomal membrane protein 11C, also known as PEX11-gamma) is the third and least
characterized member of the human PEX11 family of peroxisomal membrane proteins (PMID:12559946).
It is a multi-pass integral membrane protein of the peroxisome that promotes membrane protrusion
and elongation on the peroxisomal surface, contributing to peroxisome proliferation and
maintenance (PMID:20826455). PEX11G forms homodimers and heterodimers with PEX11A and PEX11B,
and interacts with the fission adaptors FIS1 and MFF, linking membrane elongation to the
fission machinery (PMID:20826455, PMID:22595523). The protein contains a functional amphipathic
helix that promotes membrane bending/elongation (PMID:22595523). Unlike the inducible PEX11A,
PEX11G is constitutively expressed and shows tissue-enhanced expression in liver and testis
(PMID:12559946). Overexpression of PEX11G can partially rescue peroxisome morphology defects
in PEX11B-deficient patient fibroblasts under stress conditions, suggesting functional
compensation potential among isoforms (DOI:10.3390/cells11121922).
alternative_products:
- name: '1'
id: Q96HA9-1
- name: '2'
id: Q96HA9-2
sequence_note: VSP_013539
existing_annotations:
- term:
id: GO:0005778
label: peroxisomal membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
PEX11G is well-established as a peroxisomal membrane protein. IBA annotation via
phylogenetic inference is consistent with experimental data from multiple studies
showing localization to the peroxisomal membrane (PMID:12559946, PMID:20826455,
PMID:12417726). UniProt records this as a multi-pass membrane protein of the
peroxisome membrane with evidence from three independent publications. Koch and
Brocard (PMID:22595523) further confirmed PEX11G as a true integral peroxisomal
membrane protein not extractable by sodium carbonate.
action: ACCEPT
reason: >-
Peroxisomal membrane localization is a core property of PEX11G, confirmed by
immunofluorescence colocalization with PTS1-tagged peroxisomal markers
(PMID:12559946), carbonate extraction experiments (PMID:22595523), and
additional studies (PMID:20826455, PMID:12417726). The IBA annotation is
phylogenetically sound and experimentally validated.
additional_reference_ids:
- file:human/PEX11G/PEX11G-deep-research-falcon.md
supported_by:
- reference_id: PMID:12559946
supporting_text: "Pex11pgamma was found to be a peroxisomal membrane protein, as assessed by colocalization with peroxisome targeting signal type 1 (PTS1)-proteins, in epitope-tagged Pex11pgamma-expressing Chinese hamster ovary cells."
- reference_id: PMID:20826455
supporting_text: "Dynamic changes of membrane structure are intrinsic to organelle morphogenesis and homeostasis. Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs)"
- reference_id: file:human/PEX11G/PEX11G-deep-research-falcon.md
supporting_text: "PEX11G is clearly a peroxisomal integral membrane protein with membrane-shaping motifs, and it can drive elongation when overexpressed"
- term:
id: GO:0016559
label: peroxisome fission
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
IBA annotation for peroxisome fission. PEX11 family members are established as
membrane elongation factors that coordinate peroxisome proliferation (PMID:20826455).
The Koch et al. 2010 paper demonstrates that PEX11 proteins induce formation of
juxtaposed elongated peroxisomes (JEPs) as intermediates in the peroxisome fission
process, and that FIS1 is the limiting factor for progression to fission. PEX11G
is more precisely a membrane elongation factor that acts upstream of the actual
fission event, but peroxisome fission is a reasonable annotation for the overall
process it participates in.
action: ACCEPT
reason: >-
While PEX11G is more directly involved in the membrane elongation step rather than
the fission step per se, the overall biological process of peroxisome fission
encompasses the elongation-to-division pathway. The IBA annotation appropriately
captures PEX11G involvement in this process.
supported_by:
- reference_id: PMID:20826455
supporting_text: "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."
- term:
id: GO:0005778
label: peroxisomal membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
IEA annotation for peroxisomal membrane localization via combined automated methods.
This is consistent with the experimentally validated IDA and IBA annotations for the
same term. Redundant but not incorrect.
action: ACCEPT
reason: >-
Automated annotation is consistent with all experimental evidence. Peroxisomal membrane
localization is the core cellular component for PEX11G.
- term:
id: GO:0016559
label: peroxisome fission
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
IEA annotation for peroxisome fission via InterPro-to-GO mapping. The PEX11 InterPro
domain (IPR008733) maps to this process. This is consistent with the IBA and IDA
annotations for the same term and supported by the Koch et al. 2010 experimental data.
action: ACCEPT
reason: >-
The InterPro-based annotation is correct. PEX11G belongs to the PEX11 family
(IPR008733, Pfam PF05648) which is functionally characterized as involved in
peroxisome fission/proliferation.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
review:
summary: >-
Protein binding annotation from the HuRI high-throughput yeast two-hybrid interactome
study (Luck et al. 2020, PMID:32296183). The UniProt record lists interactions with
AQP6, ERGIC3, KCNJ6, TMEM14B, and TMEM86B from IntAct with 3 experiments each. These
are all membrane proteins but none have obvious biological connection to peroxisome
biology. These interactions from a high-throughput screen likely represent
non-physiological membrane protein interactions in the Y2H system.
action: REMOVE
reason: >-
Generic protein binding is uninformative. The interactions reported from the HuRI
high-throughput Y2H screen (PMID:32296183) are with proteins that have no known
connection to peroxisome biology (AQP6 is an aquaporin, ERGIC3 is an ER-Golgi
protein, KCNJ6 is a potassium channel). These are likely artifacts of the
high-throughput assay. The biologically relevant interactions of PEX11G (with
PEX11A, PEX11B, and FIS1) are documented in PMID:20826455 but are not captured
by this annotation.
supported_by:
- reference_id: PMID:32296183
supporting_text: "HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins"
- term:
id: GO:0005778
label: peroxisomal membrane
evidence_type: IDA
original_reference_id: PMID:12559946
review:
summary: >-
Direct experimental evidence for peroxisomal membrane localization from the original
PEX11G cloning and characterization paper (Tanaka et al. 2003). The authors showed
colocalization of epitope-tagged PEX11G with PTS1-proteins in CHO cells and
demonstrated a two-transmembrane-segment topology with both N- and C-termini
facing the cytosol.
action: ACCEPT
reason: >-
This is the primary experimental evidence for PEX11G peroxisomal membrane
localization. Direct immunofluorescence and topology studies provide strong
evidence for this core annotation.
supported_by:
- reference_id: PMID:12559946
supporting_text: "Pex11pgamma was found to be a peroxisomal membrane protein, as assessed by colocalization with peroxisome targeting signal type 1 (PTS1)-proteins, in epitope-tagged Pex11pgamma-expressing Chinese hamster ovary cells. Pex11pgamma exposes both of the N- and C-terminal parts to the cytosol."
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20826455
review:
summary: >-
Protein binding annotation from Koch et al. 2010 which demonstrated homo- and
heterodimerization of PEX11 family members and interaction with the fission factor
FIS1. While the interactions are biologically meaningful, the generic term
'protein binding' fails to capture the specific nature of these interactions.
PEX11G forms homodimers and heterodimers with PEX11A and PEX11B, and interacts
with FIS1 to coordinate peroxisome elongation and fission.
action: MODIFY
reason: >-
The term 'protein binding' (GO:0005515) is too generic and uninformative. The
biologically relevant interactions are specific: homodimerization, heterodimerization
with PEX11A/PEX11B, and interaction with FIS1. These should be captured with more
specific molecular function terms.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
- id: GO:0046982
label: protein heterodimerization activity
supported_by:
- reference_id: PMID:20826455
supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
- term:
id: GO:0005777
label: peroxisome
evidence_type: IDA
original_reference_id: PMID:20826455
review:
summary: >-
Annotation to the broader term 'peroxisome' (GO:0005777) based on Koch et al. 2010.
PEX11G is more specifically localized to the peroxisomal membrane (GO:0005778), which
is a child term of peroxisome. Since the more specific term is already annotated with
both IDA and IBA evidence, this broader annotation is redundant but not incorrect.
action: ACCEPT
reason: >-
While redundant with the more specific GO:0005778 (peroxisomal membrane) annotations,
this is not incorrect. The peroxisome annotation encompasses the membrane localization.
Some annotation pipelines retain both levels.
supported_by:
- reference_id: PMID:20826455
supporting_text: "Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs)"
- term:
id: GO:0016559
label: peroxisome fission
evidence_type: IDA
original_reference_id: PMID:20826455
review:
summary: >-
Direct experimental evidence for involvement in peroxisome fission from Koch et al.
2010. The study demonstrated that ectopic expression of PEX11 family members
(including PEX11G) leads to formation of juxtaposed elongated peroxisomes (JEPs),
which are intermediates in the peroxisome fission process. Excess FIS1 fragments
these JEPs into normal round peroxisomes, demonstrating that PEX11-induced
elongation is an intermediate step in fission. This is a core function of PEX11G.
action: ACCEPT
reason: >-
Koch et al. 2010 provides direct experimental evidence that PEX11G promotes the
membrane elongation step of peroxisome fission. While PEX11G acts specifically at
the elongation stage rather than the scission step, the overall process annotation
to peroxisome fission is appropriate as the elongation is an integral part of the
fission pathway.
supported_by:
- reference_id: PMID:20826455
supporting_text: "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. Hence, we propose a model for a conserved role of PEX11 proteins in peroxisome maintenance through peroxisome polarization, membrane elongation and segregation."
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: IDA
original_reference_id: PMID:20826455
review:
summary: >-
Annotation to the generic 'protein-containing complex' term based on Koch et al.
2010, which demonstrated that PEX11G forms homodimers and heterodimers with PEX11A
and PEX11B. While the formation of these complexes is experimentally supported,
the term is extremely generic and uninformative. A more specific complex term would
be preferable but none exists in GO for PEX11 complexes.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The term 'protein-containing complex' (GO:0032991) is too broad to be informative.
While PEX11G does form homo- and heterodimeric complexes, annotating to this very
generic CC term adds little value. The specific interaction partners are better
captured through molecular function annotations (e.g., homodimerization activity).
supported_by:
- reference_id: PMID:20826455
supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
- term:
id: GO:0044375
label: regulation of peroxisome size
evidence_type: IDA
original_reference_id: PMID:20826455
review:
summary: >-
Annotation for regulation of peroxisome size based on Koch et al. 2010. PEX11G
promotes membrane elongation, which changes peroxisome morphology from round to
elongated tubular structures (JEPs). This does affect peroxisome size/shape as
an intermediate in the proliferation process. The term definition is "any process
that modulates the volume of a peroxisome," which is consistent with the membrane
elongation activity of PEX11G.
action: ACCEPT
reason: >-
PEX11G-induced membrane elongation directly modulates peroxisome size and shape,
converting round peroxisomes into elongated tubular structures. This is a core
function of PEX11G and the term accurately captures this activity.
supported_by:
- reference_id: PMID:20826455
supporting_text: "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."
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: IDA
original_reference_id: PMID:20826455
review:
summary: >-
New annotation proposed to replace the generic 'protein binding' annotation from
PMID:20826455. Koch et al. 2010 established that PEX11G forms homodimers, which
is part of its functional mechanism in membrane elongation.
action: NEW
reason: >-
Koch et al. 2010 demonstrated homodimerization of PEX11G as part of its functional
characterization. This is a more informative molecular function term than generic
protein binding.
supported_by:
- reference_id: PMID:20826455
supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
- term:
id: GO:0180020
label: membrane bending activity
evidence_type: IDA
original_reference_id: PMID:22595523
review:
summary: >-
New annotation proposed for the primary PEX11G molecular function. PEX11G
uses membrane-anchored domains and an amphipathic region to dock into the
peroxisomal membrane and regulate membrane elongation/protrusion, which is
better captured as membrane bending activity than by dimerization alone.
action: NEW
reason: >-
The core molecular activity supported by the topology and mutagenesis work
is membrane remodeling/bending during peroxisome elongation. Homo- and
heterodimerization are mechanistic supporting interactions, but membrane
bending is the most specific GO molecular function for the primary activity.
supported_by:
- reference_id: PMID:22595523
supporting_text: "we establish that the PEX11gamma sequence includes two membrane-anchored domains, which dock an amphipathic region onto the peroxisomal membrane thereby regulating its elongation"
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:12417726
title: PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate
but is dispensable for peroxisome proliferator-activated receptor alpha-mediated
peroxisome proliferation.
findings:
- statement: PEX11G identified as third mammalian PEX11 gene encoding a peroxisomal protein, with distinct expression properties from PEX11A and PEX11B
supporting_text: "we report the identification of a third mammalian PEX11 gene, PEX11 gamma, and show that it too encodes a peroxisomal protein"
- statement: PEX11G overexpression does not induce peroxisome proliferation in fibroblasts and its expression is not detectable in fibroblasts
supporting_text: "PEX11 gamma differs from PEX11 alpha and PEX11 beta in that its overexpression does not induce peroxisome proliferation, its expression is not detectable in fibroblasts, and its expression is altered neither by classical PPAs nor by the loss of PEX11 alpha or PEX11 beta"
- id: PMID:12559946
title: cDNA cloning and characterization of the third isoform of human peroxin Pex11p.
findings:
- statement: PEX11G identified as third human PEX11 isoform with 241 amino acids and two putative transmembrane segments
supporting_text: "We have cloned a human cDNA encoding an isoform of the peroxin Pex11p, termed Pex11pgamma...Pex11pgamma was 241 amino-acid long, with two putative transmembrane segments"
- statement: PEX11G shows 22-23% identity to PEX11A and PEX11B
supporting_text: "showing 22% and 23% amino-acid identity to Pex11palpha and Pex11pbeta, respectively"
- statement: PEX11G localized to peroxisomal membrane by colocalization with PTS1 markers, with both N- and C-termini facing the cytosol
supporting_text: "Pex11pgamma was found to be a peroxisomal membrane protein, as assessed by colocalization with peroxisome targeting signal type 1 (PTS1)-proteins, in epitope-tagged Pex11pgamma-expressing Chinese hamster ovary cells. Pex11pgamma exposes both of the N- and C-terminal parts to the cytosol."
- statement: PEX11G is not induced by clofibrate, showing constitutive expression similar to PEX11B
supporting_text: "PEX11gamma was not induced in rats by treatment of clofibrate, a peroxisome proliferator, similar to constitutively expressed PEX11beta but in contrast to inducible PEX11alpha."
- id: PMID:20826455
title: PEX11 family members are membrane elongation factors that coordinate peroxisome
proliferation and maintenance.
findings:
- statement: PEX11G promotes membrane protrusion and elongation on peroxisomal surface
supporting_text: "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."
- statement: PEX11G forms homodimers and heterodimers with PEX11A and PEX11B, and interacts with the fission factor FIS1
supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
- statement: JEPs are intermediates in peroxisome fission pathway with FIS1 as the limiting factor for progression
supporting_text: "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."
- id: PMID:22595523
title: PEX11 proteins attract Mff and human Fis1 to coordinate peroxisomal fission.
findings:
- statement: PEX11G membrane topology determined with two membrane-anchored domains and amphipathic region regulating elongation
supporting_text: "we establish that the PEX11gamma sequence includes two membrane-anchored domains, which dock an amphipathic region onto the peroxisomal membrane thereby regulating its elongation"
- statement: PEX11G interacts with MFF and FIS1, linking membrane elongation to fission machinery recruitment
supporting_text: "We also demonstrate the presence of the mitochondrial fission factor Mff on peroxisomes and its interaction with PEX11 proteins...PEX11 proteins attract both Mff and human Fis1 (hFis1) to their site of action"
- statement: PEX11G acts in coordination with other PEX11 proteins for membrane elongation and spatiotemporal control of peroxisome division
supporting_text: "PEX11gamma is required and acts in coordination with at least one of the other PEX11 proteins to protrude the peroxisomal membrane...the concerted interaction of PEX11 proteins provides spatiotemporal control for growth and division of peroxisomes"
- id: DOI:10.3390/cells11121922
title: Fission impossible (?) - new insights into disorders of peroxisome dynamics.
findings:
- statement: PEX11G overexpression can partially rescue catalase import defects and abnormal peroxisome morphology in PEX11B-deficient patient fibroblasts under elevated-temperature stress
supporting_text: "Carmichael et al. summarize that in PEX11B-deficient patient fibroblasts, PEX11G mRNA and protein decrease substantially at elevated temperature (40 C), and that overexpression of PEX11G can partially rescue catalase import defects and abnormal peroxisome morphology under this stress condition."
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings:
- statement: High-throughput Y2H interactome study detecting PEX11G interactions with AQP6, ERGIC3, KCNJ6, TMEM14B, and TMEM86B, which lack obvious biological relevance to peroxisome function
supporting_text: "HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins"
core_functions:
- molecular_function:
id: GO:0180020
label: membrane bending activity
description: >-
PEX11G is a peroxisomal membrane elongation factor that promotes membrane
protrusion and tubulation as an intermediate step in the peroxisome fission
pathway. It forms homodimers and heterodimers with PEX11A/PEX11B, and recruits
fission adaptors FIS1 and MFF. Its amphipathic helix inserts into the membrane
to induce bending, forming juxtaposed elongated peroxisomes (JEPs) that are
subsequently divided by the DRP1/FIS1/MFF fission machinery. Homodimerization
and heterodimerization are mechanistic supporting activities, not the primary
molecular function captured by the core-function heading.
directly_involved_in:
- id: GO:0016559
label: peroxisome fission
- id: GO:0044375
label: regulation of peroxisome size
locations:
- id: GO:0005778
label: peroxisomal membrane
supported_by:
- reference_id: PMID:20826455
supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
- reference_id: PMID:22595523
supporting_text: "we establish that the PEX11gamma sequence includes two membrane-anchored domains, which dock an amphipathic region onto the peroxisomal membrane thereby regulating its elongation"