Details for: PEX19

Gene ID: 5824

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PEX19

Ensembl ID: ENSG00000162735

Description: peroxisomal biogenesis factor 19

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • group 3 innate lymphoid cell CL0001071
    CSI 5.57
    rCSI 4.18%
    PRS 97.09
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.61
    rCSI 2.52%
    PRS 97.25
  • common myeloid progenitor CL0000049
    CSI 3.53
    rCSI 2.85%
    PRS 96.33
  • rod bipolar cell CL0000751
    CSI 3.33
    rCSI 5.99%
    PRS 92.16
  • vascular associated smooth muscle cell CL0000359
    CSI 3.27
    rCSI 10.6%
    PRS 94.68
  • pro-B cell CL0000826
    CSI 3.22
    rCSI 2.67%
    PRS 96.27
  • ON-bipolar cell CL0000749
    CSI 3.11
    rCSI 4.62%
    PRS 94.25
  • neural crest cell CL0011012
    CSI 3.09
    rCSI 2.45%
    PRS 91.82
  • hematopoietic stem cell CL0000037
    CSI 2.81
    rCSI 1.87%
    PRS 96.3
  • mesodermal cell CL0000222
    CSI 2.8
    rCSI 3.36%
    PRS 95.26
  • multi-ciliated epithelial cell CL0005012
    CSI 2.72
    rCSI 2.72%
    PRS 91.57
  • stem cell CL0000034
    CSI 2.65
    rCSI 2.55%
    PRS 93.4
  • ciliated epithelial cell CL0000067
    CSI 2.61
    rCSI 2.3%
    PRS 89.58
  • epithelial cell of lung CL0000082
    CSI 2.6
    rCSI 2.16%
    PRS 96.4
  • OFF-bipolar cell CL0000750
    CSI 2.3
    rCSI 3.14%
    PRS 93.83
  • radial glial cell CL0000681
    CSI 2.2
    rCSI 3.06%
    PRS 94.46
  • enteroendocrine cell CL0000164
    CSI 2.08
    rCSI 2.84%
    PRS 93.62
  • retina horizontal cell CL0000745
    CSI 2.08
    rCSI 3.17%
    PRS 93.51
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.03
    rCSI 1.95%
    PRS 94.49
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.86
    rCSI 3.28%
    PRS 87.48
  • club cell CL0000158
    CSI 1.78
    rCSI 2.61%
    PRS 92.94
  • type B pancreatic cell CL0000169
    CSI 1.54
    rCSI 3.4%
    PRS 95.38
  • retinal cone cell CL0000573
    CSI 1.43
    rCSI 2.3%
    PRS 90.13
  • mesenchymal cell CL0008019
    CSI 1.05
    rCSI 2.67%
    PRS 92.98
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.89
    rCSI 2.58%
    PRS 95.02
  • podocyte CL0000653
    CSI 0.87
    rCSI 3.89%
    PRS 95.51

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PEX19](/details-gene/5824), or peroxisomal biogenesis factor 19, is a 33 kDa protein essential for the formation and maintenance of peroxisomes. Functioning primarily as a cytosolic chaperone and import receptor, it recognizes and transports newly synthesized peroxisomal membrane proteins (PMPs) from the cytosol to the peroxisomal membrane ([Link](https://doi.org/10.1083/jcb.200304111)). It is considered a housekeeping gene, exhibiting broad expression across numerous cell types; however, expression data indicates particularly high significance in metabolically active cells, including immune cells like [group 3 innate lymphoid cell](/details-cell/CL0001071), progenitor cells, and specialized neuronal cells of the retina. Mutations in [PEX19](/details-gene/5824) are associated with severe peroxisome biogenesis disorders (PBDs) of the Zellweger syndrome spectrum, highlighting its critical, non-redundant role in human health ([Link](https://doi.org/10.1073/pnas.96.5.2116), OMIM: [600279](https://omim.org/entry/600279)). ## Cellular Roles and Expression Landscape The expression profile of [PEX19](/details-gene/5824) is consistent with its fundamental role in cellular metabolism, showing a ubiquitous but varied presence across tissues. **Overall**, the gene demonstrates the highest significance in a diverse array of cell types, suggesting a universally critical function with context-specific demands. The highest significance is observed in [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 5.57), suggesting a high demand for peroxisomal function in these tissue-resident immune sentinels. A broader analysis of the expression landscape reveals several key functional clusters: * **Immune System:** [PEX19](/details-gene/5824) shows high significance in various immune populations, including [plasmacytoid dendritic cell, human](/details-cell/CL0001058), [common myeloid progenitor](/details-cell/CL0000049), and [pro-B cell](/details-cell/CL0000826). This pattern may reflect the importance of peroxisomes in lipid metabolism for cell signaling, membrane synthesis during proliferation, and management of reactive oxygen species (ROS) during immune responses. * **Stem and Progenitor Cells:** Significant expression in [hematopoietic stem cell](/details-cell/CL0000037) and [neural crest cell](/details-cell/CL0011012) underscores its essential role in maintaining the metabolic integrity required for cell division, differentiation, and lineage commitment. * **Specialized Tissues:** The gene is notably significant in several types of retinal neurons, including [rod bipolar cell](/details-cell/CL0000751), [ON-bipolar cell](/details-cell/CL0000749), and [OFF-bipolar cell](/details-cell/CL0000750). This suggests a specialized requirement for peroxisomal metabolism, potentially related to the synthesis or breakdown of lipids crucial for photoreceptor function and synaptic transmission. Furthermore, its importance in [multi-ciliated epithelial cell](/details-cell/CL0005012) and [epithelial cell of lung](/details-cell/CL0000082) may be linked to cellular maintenance in high-turnover or environmentally exposed tissues. This broad yet distinct expression pattern highlights that while [PEX19](/details-gene/5824) is a core housekeeping gene, the demand for its function varies significantly, being most pronounced in cells with high metabolic, proliferative, or specialized lipid requirements. ## Pathways and Molecular Function [PEX19](/details-gene/5824) is a central player in peroxisome assembly. Its function is primarily annotated within the [Establishment of protein localization to peroxisome](/details-ontology/GO:0072663) and [Peroxisome organization](/details-ontology/GO:0007031) biological processes. As a predominantly cytosolic protein, it acts as a mobile receptor that binds newly synthesized Class I peroxisomal membrane proteins ([Link](https://doi.org/10.1083/jcb.148.5.931)). At the molecular level, its function as a [Protein carrier chaperone](/details-ontology/GO:0140597) is facilitated by its ability for [Peroxisome membrane targeting sequence binding](/details-ontology/GO:0033328). It recognizes PMPs in the cytosol, shields their hydrophobic transmembrane domains, and maintains them in an import-competent state. The PEX19-PMP complex then docks onto the peroxisomal membrane via an interaction with PEX3, a peroxisomal membrane-anchored protein ([Link](https://doi.org/10.1083/jcb.200311131)). This mechanism is a key step in the Reactome pathway [Class i peroxisomal membrane protein import](/details-pathway/R-HSA-9603798). Beyond its canonical role, [PEX19](/details-gene/5824) interacts with peroxisomal ABC transporters involved in lipid homeostasis ([Link](https://doi.org/10.1006/bbrc.2000.2572)) and has been implicated in dampening the p19ARF-p53-p21WAF1 tumor suppressor pathway, suggesting functions that extend beyond peroxisome biogenesis ([Link](https://doi.org/10.1074/jbc.c100011200)). ## Research Directions While the core function of [PEX19](/details-gene/5824) in peroxisome biogenesis is well-established, its varied expression levels across different cell types and its non-canonical interactions present several avenues for future research. 1. **Role in Immune Cell Metabolism and Function:** The high significance of [PEX19](/details-gene/5824) in [group 3 innate lymphoid cell](/details-cell/CL0001071) and other immune cells is striking. ILC3s are critical for mucosal immunity and rely heavily on lipid metabolism. A plausible hypothesis is that [PEX19](/details-gene/5824)-mediated peroxisome integrity is essential for ILC3 function, possibly by regulating the synthesis of lipid mediators or by managing oxidative stress at mucosal barriers. Disruption of [PEX19](/details-gene/5824) in these cells may therefore impair host defense. 2. **Contribution to Oncogenesis via p53 Pathway Regulation:** Research has suggested that [PEX19](/details-gene/5824) can suppress the p19ARF-p53 pathway ([Link](https://doi.org/10.1074/jbc.c100011200)). This raises the hypothesis that in certain cancers, overexpression of [PEX19](/details-gene/5824) could serve as a pro-survival mechanism by inhibiting p53-mediated apoptosis or senescence. This function may be independent of its role in peroxisome biogenesis and could represent a novel mechanism of tumor immune evasion or resistance to therapy. **Experimental Approach:** To test the hypothesis regarding the role of [PEX19](/details-gene/5824) in ILC3 function (Hypothesis 1), a conditional knockout mouse model could be generated (e.g., *Rorc*-Cre driving deletion of a floxed *Pex19* allele). ILC3s isolated from the gut lamina propria of these mice could be analyzed for peroxisome number and morphology by electron microscopy and for metabolic flux using Seahorse assays. Functionally, the ability of these cells to produce key cytokines like IL-22 and IL-17 upon stimulation would be measured by intracellular flow cytometry and ELISA. Finally, challenging the knockout mice with an enteric pathogen like *Citrobacter rodentium* would reveal the in vivo consequences of ILC3-specific peroxisome deficiency on mucosal barrier integrity and host defense. **Therapeutic Potential:** As a crucial housekeeping gene, systemic **inhibition** of [PEX19](/details-gene/5824)'s core chaperone function would likely be highly toxic, phenocopying severe peroxisome biogenesis disorders. However, if its role in suppressing the p53 pathway is validated and found to be particularly important in certain malignancies, it could represent a context-specific therapeutic target. A strategy aimed at disrupting the specific protein-protein interaction between [PEX19](/details-gene/5824) and components of the p53 pathway, while leaving its PMP-chaperone function intact, could offer a therapeutic window to restore tumor suppressor activity without causing widespread systemic toxicity.

Genular Protein ID: 3513206536

Symbol: PEX19_HUMAN

Name: 33 kDa housekeeping protein

UniProtKB Accession Codes:

P40855 D3DVE7 E9PPB4 G3V3G9 Q5QNY4 Q8NI97

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 2 CCDS 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 ELM 1 EMBL 11 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 4 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 2 Orphanet 3 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 2 UCSC 2 VEuPathDB 2 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8076834

Title: Sequence of a putative human housekeeping gene (HK33) localized on chromosome 1.

PubMed ID: 8076834

DOI: 10.1016/0378-1119(94)90308-5

PubMed ID: 9339377

Title: Genomic organization and molecular characterization of a gene encoding HsPXF, a human peroxisomal farnesylated protein.

PubMed ID: 9339377

DOI: 10.1006/geno.1997.4914

PubMed ID: 10051604

Title: Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.

PubMed ID: 10051604

DOI: 10.1073/pnas.96.5.2116

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10777694

Title: Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p.

PubMed ID: 10777694

DOI: 10.1006/bbrc.2000.2572

PubMed ID: 10704444

Title: PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.

PubMed ID: 10704444

DOI: 10.1083/jcb.148.5.931

PubMed ID: 11259404

Title: Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway.

PubMed ID: 11259404

DOI: 10.1074/jbc.c100011200

PubMed ID: 11390669

Title: Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences.

PubMed ID: 11390669

DOI: 10.1128/mcb.21.13.4413-4424.2001

PubMed ID: 11883941

Title: Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly.

PubMed ID: 11883941

DOI: 10.1006/bbrc.2002.6568

PubMed ID: 15007061

Title: PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins.

PubMed ID: 15007061

DOI: 10.1083/jcb.200311131

PubMed ID: 14709540

Title: PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.

PubMed ID: 14709540

DOI: 10.1083/jcb.200304111

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20683989

Title: A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder.

PubMed ID: 20683989

DOI: 10.1002/ajmg.a.33560

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 27181750

Title: Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response.

PubMed ID: 27181750

DOI: 10.1038/srep26028

PubMed ID: 19197237

Title: Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19.

PubMed ID: 19197237

DOI: 10.1038/emboj.2009.7

PubMed ID: 21102411

Title: Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.

PubMed ID: 21102411

DOI: 10.1038/emboj.2010.293

PubMed ID: 20554521

Title: Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19.

PubMed ID: 20554521

DOI: 10.1074/jbc.m110.138503

PubMed ID: 33798445

Title: Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.

PubMed ID: 33798445

DOI: 10.1016/j.ajhg.2021.03.013

Sequence Information:

  • Length: 299
  • Mass: 32807
  • Checksum: 399AF6B79F219100
  • Sequence:
    • MAAAEEGCSV GAEADRELEE LLESALDDFD KAKPSPAPPS TTTAPDASGP QKRSPGDTAK 
DALFASQEKF FQELFDSELA SQATAEFEKA MKELAEEEPH LVEQFQKLSE AAGRVGSDMT 
SQQEFTSCLK ETLSGLAKNA TDLQNSSMSE EELTKAMEGL GMDEGDGEGN ILPIMQSIMQ 
NLLSKDVLYP SLKEITEKYP EWLQSHRESL PPEQFEKYQE QHSVMCKICE QFEAETPTDS 
ETTQKARFEM VLDLMQQLQD LGHPPKELAG EMPPGLNFDL DALNLSGPPG ASGEQCLIM