| Name | von Hippel-Lindau tumor suppressor-like |
| Description | Von Hippel-Lindau (VHL) tumor suppressor protein is a component of an E3 ubiquitin ligase complex that selectively ubiquitinates the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor for proteasome-mediated degradation. Inactivation of VHL causes VHL disease and sporadic kidney cancer. This gene encodes a VHL homolog that lacks one of two key domains necessary for VHL function. This gene may contribute to the regulation of oxygen homeostasis and neovascularization during placenta development. This gene is intronless, and can also be interpreted as a retrotransposed pseudogene of the VHL locus located on chromosome 3. However, the protein is represented in this RefSeq due to evidence in PMID:14757845 that strongly suggests it is translated. The same publication also indicates that this protein binds HIF alpha but fails to recruit the E3 ubiquitin ligase complex, and it therefore functions as a dominant-negative VHL protein and a protector of HIF alpha. [provided by RefSeq, Jan 2010] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe mitogen‐activated protein kinase (MAPK) network orchestrates diverse cellular stress and inflammatory responses through two interlinked branches. One branch, typified by p38 MAPK and its downstream effector MAPK‐activated protein kinase‑2 (MK2), exerts critical posttranscriptional control over cytokine biosynthesis. For example, MK2 phosphorylates RNA‐binding proteins such as tristetraprolin to reduce its affinity for adenine/uridine‑rich elements in mRNAs like that of tumor necrosis factor (TNF), thereby stabilizing target messages and ensuring sustained cytokine production in response to lipopolysaccharide stimulation. In addition, MK2 can stabilize p38 MAPK itself, coordinate the remodeling of the actin cytoskeleton via substrates like heat shock protein 27, and regulate nuclear–cytoplasmic partitioning of key transcription factors to fine‑tune inflammatory gene expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA parallel regulatory arm mediated by MAPK kinases MEK1 and MEK2 activates extracellular signal‑regulated kinases (ERK1/2) to govern cell proliferation, differentiation, and survival in multiple cellular contexts. MEK/ERK signaling is instrumental in modulating antigen‐receptor responses in lymphocytes, sustaining proper developmental trajectories in placental and Leydig cells, and integrating cues from growth factors and stress signals. In many instances, the MEK/ERK cascade acts in tandem with or in opposition to the p38/MK2 pathway, thereby achieving a balance between proinflammatory outputs and the maintenance of cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThese intertwined signaling pathways have far‐reaching implications for disease pathogenesis and therapeutic intervention. In various animal models, dysregulation of the p38/MK2 and MEK/ERK modules contributes to conditions as diverse as asthma, ventilator‑induced lung injury, pancreatitis, atherosclerosis, autoimmune skin disorders, and even aberrant neuronal plasticity. Moreover, strategies targeting these kinases—including genetic ablation or pharmacological inhibitors—can modulate cytokine production, alter cell migration and apoptosis, and even restore proper progenitor cell function, highlighting their potential as drug targets in inflammatory, neoplastic, and degenerative diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael J Piatelli, Cheryl Doughty, Thomas C Chiles "}, {"type": "b", "children": [{"type": "t", "text": "Requirement for a hsp90 chaperone-dependent MEK1/2-ERK pathway for B cell antigen receptor-induced cyclin D2 expression in mature B lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200102200"}], "href": "https://doi.org/10.1074/jbc.M200102200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11823472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11823472"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexey Kotlyarov, Yvonne Yannoni, Susann Fritz, et al. 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| Synonyms | VLP, VHLP |
| Proteins | VHLL_HUMAN |
| NCBI Gene ID | 391104 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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VHLL has 937 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 40 datasets.
Click the + buttons to view associations for VHLL from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by VHLL gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of VHLL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of VHLL gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of VHLL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of VHLL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of VHLL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of VHLL gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with VHLL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of VHLL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with VHLL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with VHLL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with VHLL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with VHLL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with VHLL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at VHLL gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of VHLL gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of VHLL gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of VHLL gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of VHLL gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of VHLL gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of VHLL gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by VHLL gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of VHLL gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of VHLL gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with VHLL gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of VHLL gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for VHLL protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of VHLL gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of VHLL gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of VHLL gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain VHLL protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by VHLL gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for VHLL from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of VHLL gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of VHLL gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of VHLL gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of VHLL gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of VHLL gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of VHLL gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with VHLL protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
