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UniProtKB - P40337 (VHL_HUMAN)

Entry version 224 (18 Sep 2019)
Sequence version 2 (15 Dec 1998)
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Protein

von Hippel-Lindau disease tumor suppressor

Gene

VHL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-3232142 SUMOylation of ubiquitinylation proteins
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

SIGNOR Signaling Network Open Resource

More...SIGNORi		P40337

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...UniPathwayi		UPA00143

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
von Hippel-Lindau disease tumor suppressor
Alternative name(s):
Protein G7
pVHL
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:VHL
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 3

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:12687 VHL

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		608537 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P40337

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Pheochromocytoma (PCC)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
Related information in OMIM
von Hippel-Lindau disease (VHLD)18 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionVHLD is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst).
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00567038S → P in VHLD; type II. 1 Publication1
Natural variantiVAR_00567152E → K in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs373068386EnsemblClinVar.1
Natural variantiVAR_00567265S → L in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs5030826EnsemblClinVar.1
Natural variantiVAR_00567365S → W in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs5030826EnsemblClinVar.1
Natural variantiVAR_00567466 – 73Missing in VHLD; type I. 8
Natural variantiVAR_00567568S → W in pheochromocytoma and VHLD; type II. 2 Publications1
Natural variantiVAR_00567670E → K in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030802EnsemblClinVar.1
Natural variantiVAR_00567774V → G in VHLD; type I-II. 1 PublicationCorresponds to variant dbSNP:rs5030803Ensembl.1
Natural variantiVAR_03499075Missing in VHLD. 1 Publication1
Natural variantiVAR_00567976F → I in VHLD; type I. 1 Publication1
Natural variantiVAR_00568076F → L in VHLD; type I. 1 Publication1
Natural variantiVAR_00568176F → S in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882033EnsemblClinVar.1
Natural variantiVAR_00567876Missing in VHLD; type I; common mutation. 1 Publication1
Natural variantiVAR_00568278N → H in VHLD; type I. 1 Publication1
Natural variantiVAR_00568378N → S in VHLD; type I; common mutation. 1 PublicationCorresponds to variant dbSNP:rs5030804EnsemblClinVar.1
Natural variantiVAR_00568478N → T in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030804EnsemblClinVar.1
Natural variantiVAR_00568579R → P in VHLD. 1
Natural variantiVAR_00568680S → I in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030805Ensembl.1
Natural variantiVAR_00568880S → N in pheochromocytoma and VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs5030805Ensembl.1
Natural variantiVAR_00568780S → R in VHLD; type I. 2 Publications1
Natural variantiVAR_00568981P → S in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs104893829EnsemblClinVar.1
Natural variantiVAR_00569182 – 84Missing in VHLD. 3
Natural variantiVAR_00569082R → P in VHLD; type I. Corresponds to variant dbSNP:rs794726890EnsemblClinVar.1
Natural variantiVAR_00569284V → L in VHLD; type II and type 2C. 2 PublicationsCorresponds to variant dbSNP:rs5030827EnsemblClinVar.1
Natural variantiVAR_00569386P → A in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs398123481EnsemblClinVar.1
Natural variantiVAR_00809786P → H in VHLD. 1
Natural variantiVAR_00569486P → L in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882034EnsemblClinVar.1
Natural variantiVAR_00569586P → R in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882034EnsemblClinVar.1
Natural variantiVAR_00569686P → S in VHLD. 2 PublicationsCorresponds to variant dbSNP:rs398123481EnsemblClinVar.1
Natural variantiVAR_00569788W → R in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs1553619431EnsemblClinVar.1
Natural variantiVAR_00569888W → S in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs119103277EnsemblClinVar.1
Natural variantiVAR_00570089L → P in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030807EnsemblClinVar.1
Natural variantiVAR_00570292 – 97Missing in VHLD; type I. 6
Natural variantiVAR_00570393G → C in pheochromocytoma and VHLD; type II. 2 PublicationsCorresponds to variant dbSNP:rs5030808EnsemblClinVar.1
Natural variantiVAR_00570493G → D in VHLD. Corresponds to variant dbSNP:rs1553619440EnsemblClinVar.1
Natural variantiVAR_00570593G → S in pheochromocytoma and VHLD; type II. 1 PublicationCorresponds to variant dbSNP:rs5030808EnsemblClinVar.1
Natural variantiVAR_00570696Q → P in VHLD; type I. 1 Publication1
Natural variantiVAR_00570798Y → H in pheochromocytoma and VHLD; type II. 1 PublicationCorresponds to variant dbSNP:rs5030809EnsemblClinVar.1
Natural variantiVAR_005708101L → G in VHLD; type I; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_005709101L → R in VHLD; type I. 1 Publication1
Natural variantiVAR_005711105T → P in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs1553619461EnsemblClinVar.1
Natural variantiVAR_005713107R → P in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs193922609EnsemblClinVar.1
Natural variantiVAR_005714111S → C in VHLD; type II. 1
Natural variantiVAR_005715111S → N in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs869025631EnsemblClinVar.1
Natural variantiVAR_005716111S → R in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs765978945EnsemblClinVar.1
Natural variantiVAR_005717112Y → H in VHLD; type IIA. Corresponds to variant dbSNP:rs104893824EnsemblClinVar.1
Natural variantiVAR_034992112Y → N in VHLD. 1 PublicationCorresponds to variant dbSNP:rs104893824EnsemblClinVar.1
Natural variantiVAR_005718114G → C in VHLD; type II. 1 Publication1
Natural variantiVAR_005719114G → R in VHLD; type I-II. Corresponds to variant dbSNP:rs869025636EnsemblClinVar.1
Natural variantiVAR_005720114G → S in VHLD; type II. 1 Publication1
Natural variantiVAR_005723115H → Q in VHLD; type II. 1 Publication1
Natural variantiVAR_008098115H → R in VHLD; type II. Corresponds to variant dbSNP:rs5030812Ensembl.1
Natural variantiVAR_005722115H → Y in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030811Ensembl.1
Natural variantiVAR_005724116L → V in VHLD. 1 Publication1
Natural variantiVAR_005725117W → C in VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs727504215EnsemblClinVar.1
Natural variantiVAR_005726118L → P in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs5030830EnsemblClinVar.1
Natural variantiVAR_005727118L → R in VHLD. 1 PublicationCorresponds to variant dbSNP:rs5030830EnsemblClinVar.1
Natural variantiVAR_005728119F → L in pheochromocytoma and VHLD; type II. 1 PublicationCorresponds to variant dbSNP:rs1553619948EnsemblClinVar.1
Natural variantiVAR_005729119F → S in VHLD; type II. 1 Publication1
Natural variantiVAR_005730121D → G in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030832EnsemblClinVar.1
Natural variantiVAR_005731128L → F in VHLD; type II. Corresponds to variant dbSNP:rs1553619956EnsemblClinVar.1
Natural variantiVAR_005732129L → LE in VHLD. 1
Natural variantiVAR_005733130V → L in ECYT2 and VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs104893830EnsemblClinVar.1
Natural variantiVAR_005734131N → K in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs1064794272EnsemblClinVar.1
Natural variantiVAR_005735131N → T in VHLD; type I. 1 Publication1
Natural variantiVAR_005737136F → C in pheochromocytoma and VHLD; type II. 1 PublicationCorresponds to variant dbSNP:rs5030833EnsemblClinVar.1
Natural variantiVAR_005736136F → S in VHLD. 1 PublicationCorresponds to variant dbSNP:rs5030833EnsemblClinVar.1
Natural variantiVAR_008099136F → Y in VHLD. 1
Natural variantiVAR_005738143D → E in VHLD; type II. 1 Publication1
Natural variantiVAR_008100145Q → H in VHLD. Corresponds to variant dbSNP:rs771727849EnsemblClinVar.1
Natural variantiVAR_005739148Missing in VHLD; type I. 1
Natural variantiVAR_005740149A → T in VHLD; type II. 1 PublicationCorresponds to variant dbSNP:rs587780077EnsemblClinVar.1
Natural variantiVAR_005741154P → L in VHLD; type II. 1
Natural variantiVAR_005742155V → G in VHLD; type II. 1 Publication1
Natural variantiVAR_008101155V → M in VHLD; with RCC. Corresponds to variant dbSNP:rs869025659EnsemblClinVar.1
Natural variantiVAR_005743156Y → C in pheochromocytoma and VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs397516441EnsemblClinVar.1
Natural variantiVAR_005744156Y → D in VHLD; type I. 1 Publication1
Natural variantiVAR_005746157T → I in VHLD; type II. 2 PublicationsCorresponds to variant dbSNP:rs869025660EnsemblClinVar.1
Natural variantiVAR_005747157T → TF in VHLD; type I. 1
Natural variantiVAR_005748158L → P in VHLD; type I-II; abolishes release from chaperonin complex and the interaction with Elongin BC complex. 3 PublicationsCorresponds to variant dbSNP:rs121913346EnsemblClinVar.1
Natural variantiVAR_005749158L → V in VHLD; type I. 1 Publication1
Natural variantiVAR_005750159K → E in VHLD; type II. 1
Natural variantiVAR_005753161R → G in VHLD; type II. Corresponds to variant dbSNP:rs5030818Ensembl.1
Natural variantiVAR_005752161R → P in pheochromocytoma and VHLD; type I. 2 Publications1
Natural variantiVAR_005751161R → Q in pheochromocytoma and VHLD; type II. 2 PublicationsCorresponds to variant dbSNP:rs730882035EnsemblClinVar.1
Natural variantiVAR_005754162C → F in VHLD; type I; No effect on interaction with HIF1A nor on HIF1A degradation. 4 PublicationsCorresponds to variant dbSNP:rs397516444EnsemblClinVar.1
Natural variantiVAR_005755162C → R in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs1553620313EnsemblClinVar.1
Natural variantiVAR_005756162C → W in VHLD; type I-II. 2 PublicationsCorresponds to variant dbSNP:rs869025662Ensembl.1
Natural variantiVAR_005757162C → Y in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs397516444EnsemblClinVar.1
Natural variantiVAR_008102164Q → H in VHLD. Corresponds to variant dbSNP:rs1352275281EnsemblClinVar.1
Natural variantiVAR_005758164Q → R in VHLD; type II. 2 PublicationsCorresponds to variant dbSNP:rs267607170EnsemblClinVar.1
Natural variantiVAR_008103166V → D in VHLD; with RCC. 1
Natural variantiVAR_005759166V → F in VHLD; type IIA. 2 PublicationsCorresponds to variant dbSNP:rs104893825EnsemblClinVar.1
Natural variantiVAR_005760167R → G in VHLD; type I-II. 1 PublicationCorresponds to variant dbSNP:rs5030820EnsemblClinVar.1
Natural variantiVAR_005761167R → Q in pheochromocytoma and VHLD; type II; common mutation. 3 PublicationsCorresponds to variant dbSNP:rs5030821EnsemblClinVar.1
Natural variantiVAR_005762167R → W in pheochromocytoma and VHLD; type II; common mutation. 4 PublicationsCorresponds to variant dbSNP:rs5030820EnsemblClinVar.1
Natural variantiVAR_005763170V → D in VHLD; type II. 1 Publication1
Natural variantiVAR_005764170V → F in VHLD; type II. 1
Natural variantiVAR_005765170V → G in VHLD; type I. 2 Publications1
Natural variantiVAR_005766175Y → D in VHLD; type I. 1 Publication1
Natural variantiVAR_008104176R → W in VHLD. 1
Natural variantiVAR_005767177R → RLRVKPE in VHLD; type I. 1
Natural variantiVAR_005768178L → P in VHLD; type I-II; common mutation. 1 PublicationCorresponds to variant dbSNP:rs5030822EnsemblClinVar.1
Natural variantiVAR_005769178L → Q in VHLD; type II. Corresponds to variant dbSNP:rs5030822EnsemblClinVar.1
Natural variantiVAR_005770180I → V in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs377715747EnsemblClinVar.1
Natural variantiVAR_005772184L → P in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs1064793878EnsemblClinVar.1
Natural variantiVAR_005771184L → R in VHLD; type I. 1 Publication1
Natural variantiVAR_005773186E → K in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs367545984EnsemblClinVar.1
Natural variantiVAR_005774186Missing in VHLD. 1 Publication1
Natural variantiVAR_005775188L → P in VHLD; type I-II. 1 Publication1
Natural variantiVAR_005776188L → Q in VHLD; type I. 1 Publication1
Natural variantiVAR_005777188L → V in ECYT2, pheochromocytoma and VHLD; type IIA. 2 PublicationsCorresponds to variant dbSNP:rs5030824EnsemblClinVar.1
Natural variantiVAR_005778198L → R in ECYT2 and VHLD; type II. 1
Natural variantiVAR_005779200R → W in ECYT2 and VHLD; type I. 4 PublicationsCorresponds to variant dbSNP:rs28940298EnsemblClinVar.1
Erythrocytosis, familial, 2 (ECYT2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034994126D → Y in ECYT2. 1 PublicationCorresponds to variant dbSNP:rs104893831EnsemblClinVar.1
Natural variantiVAR_005733130V → L in ECYT2 and VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs104893830EnsemblClinVar.1
Natural variantiVAR_005777188L → V in ECYT2, pheochromocytoma and VHLD; type IIA. 2 PublicationsCorresponds to variant dbSNP:rs5030824EnsemblClinVar.1
Natural variantiVAR_034999191H → D in ECYT2. 1 PublicationCorresponds to variant dbSNP:rs28940301EnsemblClinVar.1
Natural variantiVAR_035000192P → S in ECYT2. 1 PublicationCorresponds to variant dbSNP:rs28940300EnsemblClinVar.1
Natural variantiVAR_005778198L → R in ECYT2 and VHLD; type II. 1
Natural variantiVAR_005779200R → W in ECYT2 and VHLD; type I. 4 PublicationsCorresponds to variant dbSNP:rs28940298EnsemblClinVar.1
Renal cell carcinoma (RCC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRenal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034998163L → P in RCC; with paraneoplastic erythrocytosis; inhibits binding to HIF1AN. 2 PublicationsCorresponds to variant dbSNP:rs28940297EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi98Y → N: No interaction with HIF1A. No HIF1A degradation. 1 Publication1

Keywords - Diseasei

Congenital erythrocytosis, Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNET

More...DisGeNETi		7428

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		VHL

MalaCards human disease database

More...MalaCardsi		VHL
MIMi144700 phenotype
171300 phenotype
193300 phenotype
263400 phenotype

Open Targets

More...OpenTargetsi		ENSG00000134086

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		238557 Chuvash erythrocytosis
29072 Hereditary pheochromocytoma-paraganglioma
276624 Sporadic pheochromocytoma
892 Von Hippel-Lindau disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA37307

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3108660

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		VHL

Domain mapping of disease mutations (DMDM)

More...DMDMi		4033778

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000658091 – 213von Hippel-Lindau disease tumor suppressorAdd BLAST213

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P40337

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P40337

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P40337

MaxQB - The MaxQuant DataBase

More...MaxQBi		P40337

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P40337

PeptideAtlas

More...PeptideAtlasi		P40337

PRoteomics IDEntifications database

More...PRIDEi		P40337

ProteomicsDB human proteome resource

More...ProteomicsDBi		55362 [P40337-1]
55363 [P40337-2]
55364 [P40337-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P40337

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P40337

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in the adult and fetal brain and kidney.

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis and lung. Differentially expressed within renal tubules.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000134086 Expressed in 139 organ(s), highest expression level in leukocyte

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P40337 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P40337 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB005430
HPA031631
HPA031632

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins.

Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex.

Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiquitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal.

Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased.

Interacts with RNF139, USP33 and JADE1.

Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains).

Interacts with EPAS1.

Interacts with CARD9.

16 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		113269, 382 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P40337

Database of interacting proteins

More...DIPi		DIP-32585N

Protein interaction database and analysis system

More...IntActi		P40337, 68 interactors

Molecular INTeraction database

More...MINTi		P40337

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000256474

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P40337

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1213
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P40337

Database of comparative protein structure models

More...ModBasei		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P40337

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati14 – 1815
Repeati19 – 2325
Repeati24 – 2835
Repeati29 – 3345
Repeati34 – 3855
Repeati39 – 4365
Repeati44 – 4875
Repeati49 – 5385

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni14 – 538 X 5 AA tandem repeats of G-[PAVG]-E-E-[DAYSLE]Add BLAST40
Regioni100 – 155Involved in binding to CCT complexAdd BLAST56
Regioni157 – 166Interaction with Elongin BC complex10

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x3-C-x3-[AILV].

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the VHL family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG4710 Eukaryota
ENOG4111PRU LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00390000014353

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000030904

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P40337

KEGG Orthology (KO)

More...KOi		K03871

Identification of Orthologs from Complete Genome Data

More...OMAi		VGHPWMF

Database of Orthologous Groups

More...OrthoDBi		1307987at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P40337

TreeFam database of animal gene trees

More...TreeFami		TF318985

Family and domain databases

Conserved Domains Database

More...CDDi		cd05468 pVHL, 1 hit

Database of protein disorder

More...DisProti		DP00287

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.750.10, 1 hit
2.60.40.780, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR002714 VHL
IPR024048 VHL_alpha_dom
IPR037139 VHL_alpha_dom_sf
IPR024053 VHL_beta_dom
IPR037140 VHL_beta_dom_sf
IPR036208 VHL_sf
IPR022772 VHL_tumour_suppress_b/a_dom

The PANTHER Classification System

More...PANTHERi		PTHR15160:SF14 PTHR15160:SF14, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF01847 VHL, 1 hit
PF17211 VHL_C, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF49468 SSF49468, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket
Isoform 1 (identifier: P40337-1) [UniParc]FASTAAdd to basket
Also known as: VHL30, VHLp24(MPR)

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA 
        60         70         80         90        100
EEEMEAGRPR PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT 
       110        120        130        140        150
LPPGTGRRIH SYRGHLWLFR DAGTHDGLLV NQTELFVPSL NVDGQPIFAN 
       160        170        180        190        200
ITLPVYTLKE RCLQVVRSLV KPENYRRLDI VRSLYEDLED HPNVQKDLER 
       210 
LTQERIAHQR MGD
Note: Major isoform.
Length:213
Mass (Da):24,153
Last modified:December 15, 1998 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iBA5D6765FBC16EA7
GO
Isoform 2 (identifier: P40337-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-154: Missing.

Show »
Length:172
Mass (Da):19,654
Checksum:i46E2C22E8C98393D
GO
Isoform 3 (identifier: P40337-3) [UniParc]FASTAAdd to basket
Also known as: VHL19, VHLp18(MEA)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.

Note: Produced by alternative initiation at Met-54 of isoform 1.
Show »
Length:160
Mass (Da):18,532
Checksum:i2644C3B8C3A87D64
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03456225P → L in pheochromocytoma. 3 PublicationsCorresponds to variant dbSNP:rs35460768EnsemblClinVar.1
Natural variantiVAR_00567038S → P in VHLD; type II. 1 Publication1
Natural variantiVAR_00567152E → K in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs373068386EnsemblClinVar.1
Natural variantiVAR_03498763L → P in pheochromocytoma. 1 PublicationCorresponds to variant dbSNP:rs104893827EnsemblClinVar.1
Natural variantiVAR_03498864R → P in pheochromocytoma. 1 PublicationCorresponds to variant dbSNP:rs104893826EnsemblClinVar.1
Natural variantiVAR_03498965S → A in pheochromocytoma. 1 PublicationCorresponds to variant dbSNP:rs869025616EnsemblClinVar.1
Natural variantiVAR_00567265S → L in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs5030826EnsemblClinVar.1
Natural variantiVAR_00567365S → W in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs5030826EnsemblClinVar.1
Natural variantiVAR_00567466 – 73Missing in VHLD; type I. 8
Natural variantiVAR_00567568S → W in pheochromocytoma and VHLD; type II. 2 Publications1
Natural variantiVAR_00567670E → K in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030802EnsemblClinVar.1
Natural variantiVAR_00567774V → G in VHLD; type I-II. 1 PublicationCorresponds to variant dbSNP:rs5030803Ensembl.1
Natural variantiVAR_03499075Missing in VHLD. 1 Publication1
Natural variantiVAR_00567976F → I in VHLD; type I. 1 Publication1
Natural variantiVAR_00568076F → L in VHLD; type I. 1 Publication1
Natural variantiVAR_00568176F → S in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882033EnsemblClinVar.1
Natural variantiVAR_00567876Missing in VHLD; type I; common mutation. 1 Publication1
Natural variantiVAR_00568278N → H in VHLD; type I. 1 Publication1
Natural variantiVAR_00568378N → S in VHLD; type I; common mutation. 1 PublicationCorresponds to variant dbSNP:rs5030804EnsemblClinVar.1
Natural variantiVAR_00568478N → T in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030804EnsemblClinVar.1
Natural variantiVAR_00568579R → P in VHLD. 1
Natural variantiVAR_00568680S → I in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs5030805Ensembl.1
Natural variantiVAR_00568880S → N in pheochromocytoma and VHLD; type I. 3 PublicationsCorresponds to variant dbSNP:rs5030805Ensembl.1
Natural variantiVAR_00568780S → R in VHLD; type I. 2 Publications1
Natural variantiVAR_00568981P → S in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs104893829EnsemblClinVar.1
Natural variantiVAR_00569182 – 84Missing in VHLD. 3
Natural variantiVAR_00569082R → P in VHLD; type I. Corresponds to variant dbSNP:rs794726890EnsemblClinVar.1
Natural variantiVAR_00569284V → L in VHLD; type II and type 2C. 2 PublicationsCorresponds to variant dbSNP:rs5030827EnsemblClinVar.1
Natural variantiVAR_00569386P → A in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs398123481EnsemblClinVar.1
Natural variantiVAR_00809786P → H in VHLD. 1
Natural variantiVAR_00569486P → L in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882034EnsemblClinVar.1
Natural variantiVAR_00569586P → R in VHLD; type I. 1 PublicationCorresponds to variant dbSNP:rs730882034EnsemblClinVar.1
Natural variantiVAR_00569686P → S in VHLD. 2 PublicationsCorresponds to variant dbSNP:rs398123481EnsemblClinVar.1
Natural variantiVAR_00569788W → R in VHLD; type I. 2 PublicationsCorresponds to variant dbSNP:rs1553619431EnsemblClinVar.1
Natural variantiVAR_00569888W → S in VHLD; type I. 2 Publications