Search results for VHL

Showing 26 results out of 44

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Types

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Protein (5 results from a total of 6)

VHL

Identifier: R-HSA-391423
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: VHL: P40337

VHL

Identifier: R-HSA-1234127
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P40337
Identifier: R-HSA-4551697
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: VHL: P40337
Identifier: R-HSA-4551713
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P63165
Identifier: R-HSA-4551632
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P63165

Interactor (4 results from a total of 4)

VHL

Identifier: P40337-2
Species: Homo sapiens
Primary external reference: UniProt: P40337-2

VHL

Identifier: P40337-3
Species: Homo sapiens
Primary external reference: UniProt: P40337-3

VHL

Identifier: P40337-1
Species: Homo sapiens
Primary external reference: UniProt: P40337-1
Identifier: Q6RSH7
Species: Homo sapiens
Primary external reference: UniProt: Q6RSH7

Reaction (5 results from a total of 19)

Identifier: R-HSA-4551721
Species: Homo sapiens
Compartment: nucleoplasm
PIAS4 SUMOylates VHL at lysine-159, lysine-171, and lysine-196 with SUMO1 (Cai et al. 2010, Cai and Robertson 2010, Chien et al. 2013). SUMOylation facilitates the oligomerization of VHL, abolishes the inhibitory function of VHL on HIF1A, and abolishes the tumor suppressor function of VHL by inactivating the ubiquitinylation activity of VHL.
Identifier: R-HSA-9683455
Species: Homo sapiens
Compartment: cytosol
Human von Hippel Lindau (VHL) protein, a tumor suppressor that acts as a component of an E3 ubiquitin ligase complex, interacts with the non-structural protein 16 (nsp16) of the human SARS coronavirus 1 (SARS-CoV-1) and the mouse hepatitis virus, also a coronavirus. VHL negatively regulates SARS-CoV-1 replication, but the exact mechanism is not known (Yu et al. 2015).
Identifier: R-HSA-9694520
Species: Homo sapiens
Compartment: cytosol
This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

Human von Hippel Lindau (VHL) protein, a tumor suppressor that acts as a component of an E3 ubiquitin ligase complex, interacts with the non-structural protein 16 (nsp16) of the human SARS coronavirus 1 (SARS-CoV-1) and the mouse hepatitis virus, also a coronavirus. VHL negatively regulates SARS-CoV-1 replication, but the exact mechanism is not known (Yu et al. 2015).
Identifier: R-HSA-8956099
Species: Homo sapiens
Compartment: cytosol
The best characterized CRL2 substrate binding F-box protein is the von Hippel- Lindau (VHL) tumor suppressor, which targets the alpha subunit of hypoxia inducible factor (HIFalpha) for ubiquitination and degradation through VCP/p97 and the 26 S proteasome (Sufan and Ohh, 2006; Heir et al, 2013; reviewed in Cai and Yang, 2016). UBXN7 is an adapter that binds to neddylated CUL2 and interferes with the ability of the CUL2:EloB:EloC:VHL E3 ubiquitin ligase complex to ubiquitinate HIF alpha, in this way causing accumulation of HIF alpha (Bandau et al, 2012; Den Besten et al, 2012)
Identifier: R-HSA-1234183
Species: Homo sapiens
Compartment: cytosol
VHL within the VHL:ElonginB:ElonginC:CUL2:RBX1 Complex binds HIF-alpha subunits that have hydroxylated proline residues (Cockman et al. 2000, Ohh et al. 2000, Tanimoto et al. 2000, Jaakkola et al. 2001, Ivan et al. 2001, Yu et al. 2001). VHL constitutively shuttles between the cytosol and nucleoplasm (Lewis and Roberts 2003) and though the VHL:HIF-alpha complex is predominantly nuclear, binding and degradation can occur in both the cytosol and the nucleus (Berra et al. 2001).

Complex (5 results from a total of 8)

Identifier: R-HSA-4551704
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9683453
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9694398
Species: Homo sapiens
Compartment: cytosol
This COVID-19 Complex instance was generated via electronic inference from a curated CoV-1 (Human SARS coronavirus) Reactome instance. In Reactome, inference is the process used to automatically create orthologous Pathways, Reactions and PhysicalEntities from our expertly curated data (https://reactome.org/documentation/inferred-events).
Identifier: R-HSA-976093
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-1234141
Species: Homo sapiens
Compartment: nucleoplasm

Set (4 results from a total of 4)

Identifier: R-HSA-8932471
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8932465
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8932481
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8863155
Species: Homo sapiens
Compartment: cytosol
The CUL5-box was initially identified as the SOCS-box in Suppressor of Cytokine Signaling proteins. It has since been identified in numerous other protiens including the ankyrin and SOCS-box (ASB) proteins and others (Mahrour et al. 2008).

Pathway (3 results from a total of 3)

Identifier: R-HSA-1234176
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
HIF-alpha subunits, comprising HIF1A (Bruick and McKnight 2001, Ivan et al. 2001, Jaakkola et al. 2001), HIF2A (Percy et al. 2008, Furlow et al. 2009), and HIF3A (Maynard et al. 2003), are hydroxylated at proline residues by the prolyl hydroxylases PHD1 (EGLN2), PHD2 (EGLN1), and PHD3 (EGLN3) (Bruick and McKnight 2001, Berra et al. 2003, Hirsila et al. 2003, Metzen et al. 2003, Tuckerman et al. 2004, Appelhoff et al. 2004, Fedulova et al. 2007, Tian et al. 2011). The reaction requires molecular oxygen as a substrate and so it is inhibited by hypoxia. PHD2 (EGLN1) is predominantly cytosolic (Metzen et al. 2003) and is the key determinant in the regulation of HIF-alpha subunits by oxygen (Berra et al. 2003).
HIF-alpha subunits hydroxylated at proline residues are bound by VHL, an E3 ubiquitin ligase in a complex containing ElonginB, Elongin C, CUL2, and RBX1. VHL ubiquitinates HIF-alpha, resulting in destruction of HIF-alpha by proteolysis. Hypoxia inhibits proline hydroxylation and interaction with VHL, stabilizing HIF-alpha, which transits to the nucleus and activates gene expression.
Identifier: R-HSA-3232142
Species: Homo sapiens
Compartment: nucleoplasm
Several ubiquitin E3 ligases are regulated by SUMOylation (reviewed in Wilson and Heaton 2008). SUMOylation appears to be necessary for nuclear import of MDM2, the E3 ligase that ubiquitinylates TP53 (p53). SUMOylation of VHL abolishes its ubiquitin ligase activity. HERC2, RNF168, and BRCA1 are ubiquitin ligases that are SUMOylated during DNA damage response and repair.
Identifier: R-HSA-1234174
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
Oxygen plays a central role in the functioning of human cells: it is both essential for normal metabolism and toxic. Here we have annotated one aspect of cellular responses to oxygen, the role of hypoxia-inducible factor in regulating cellular transcriptional responses to changes in oxygen availability.

In the presence of oxygen members of the transcription factor family HIF-alpha, comprising HIF1A, HIF2A (EPAS1), and HIF3A, are hydroxylated on proline residues by PHD1 (EGLN2), PHD2 (EGLN1), and PHD3 (EGLN3) and on asparagine residues by HIF1AN (FIH) (reviewed in Pouyssegur et al. 2006, Semenza 2007, Kaelin and Ratcliffe 2008, Nizet and Johnson 2009, Brahimi-Horn and Pouyssegur 2009, Majmundar et al. 2010, Loenarz and Schofield 2011). Both types of reaction require molecular oxygen as a substrate and it is probable that at least some HIF-alpha molecules carry both hydroxylated asparagine and hydroxylated proline (Tian et al. 2011).
Hydroxylated asparagine interferes with the ability of HIF-alpha to interact with p300 and CBP while hydroxylated proline facilitates the interaction of HIF-alpha with the E3 ubiquitin ligase VHL, causing ubiquitination and proteolysis of HIF-alpha. Hypoxia inhibits both types of hydroxylation, resulting in the stabilization of HIF-alpha, which then enters the nucleus, binds HIF-beta, and recruits p300 and CBP to activate target genes such as EPO and VEGF.

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