Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Von Hippel-Lindau disease tumor suppressor

Gene

Vhl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as 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 (By similarity).By similarity

Pathwayi

GO - Molecular functioni

  1. enzyme binding Source: MGI
  2. protein complex binding Source: MGI
  3. transcription factor binding Source: MGI
  4. ubiquitin protein ligase activity Source: MGI

GO - Biological processi

  1. angiogenesis Source: MGI
  2. blood vessel endothelial cell migration Source: MGI
  3. extracellular matrix organization Source: MGI
  4. negative regulation of thymocyte apoptotic process Source: MGI
  5. negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: MGI
  6. neuron differentiation Source: Ensembl
  7. NLS-bearing protein import into nucleus Source: MGI
  8. positive regulation of transcription, DNA-templated Source: MGI
  9. proteasomal protein catabolic process Source: MGI
  10. protein catabolic process Source: MGI
  11. protein heterooligomerization Source: Ensembl
  12. protein transport Source: MGI
  13. protein ubiquitination Source: MGI
  14. regulation of apoptotic signaling pathway Source: MGI
  15. regulation of catecholamine metabolic process Source: Ensembl
  16. regulation of thymocyte apoptotic process Source: MGI
  17. regulation of transcription, DNA-templated Source: MGI
  18. response to ethanol Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
pVHL
Gene namesi
Name:Vhl
Synonyms:Vhlh
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:103223. Vhl.

Subcellular locationi

Cytoplasm By similarity. Membrane By similarity; Peripheral membrane protein By similarity. Nucleus By similarity
Note: Colocalizes with ADRB2 at the cell membrane.By similarity

GO - Cellular componenti

  1. cilium Source: MGI
  2. Cul2-RING ubiquitin ligase complex Source: MGI
  3. cytoplasm Source: MGI
  4. cytosol Source: Ensembl
  5. intermediate filament cytoskeleton Source: MGI
  6. membrane Source: UniProtKB-SubCell
  7. mitochondrion Source: Ensembl
  8. nucleolus Source: MGI
  9. nucleoplasm Source: MGI
  10. nucleus Source: MGI
  11. VCB complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181Von Hippel-Lindau disease tumor suppressorPRO_0000065810Add
BLAST

Proteomic databases

MaxQBiP40338.
PaxDbiP40338.
PRIDEiP40338.

PTM databases

PhosphoSiteiP40338.

Expressioni

Developmental stagei

Expressed throughout fetal nephrogenesis, abdominal and thoracic organogenesis, and nervous system development between day 10.5 and day 16.5. In the developing lung, differential expression within the endodermally derived cuboidal epithelial lining of the terminal and respiratory bronchioles. In the developing eye, high expression in both the inner and outer neuroblastic layers of the retina and lens.1 Publication

Gene expression databases

BgeeiP40338.
ExpressionAtlasiP40338. baseline and differential.
GenevestigatoriP40338.

Interactioni

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 ubiqitination 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 (By similarity). Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Interacts with LIMD1 (via LIM zinc-binding 2). Interacts with AJUBA (via LIM domains) and WTIP (via LIM domains) (By similarity). Interacts with EPAS1. Interacts with CARD9 (By similarity).By similarity

Protein-protein interaction databases

BioGridi204518. 8 interactions.
IntActiP40338. 7 interactions.
STRINGi10090.ENSMUSP00000039418.

Structurei

Secondary structure

1
181
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi124 – 13613Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HV2NMR-B123-137[»]
ProteinModelPortaliP40338.
SMRiP40338. Positions 28-170.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni123 – 13210Interaction with Elongin BC complexBy similarity

Domaini

The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].

Phylogenomic databases

eggNOGiNOG327868.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiP40338.
KOiK03871.
OMAiVGHPWMF.
OrthoDBiEOG7VMP7B.
PhylomeDBiP40338.
TreeFamiTF318985.

Family and domain databases

Gene3Di1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProiIPR002714. VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERiPTHR15160:SF0. PTHR15160:SF0. 1 hit.
PfamiPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMiSSF49468. SSF49468. 1 hit.

Sequencei

Sequence statusi: Complete.

P40338-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPRKAASPEE AAGEPGPEEM EAGRPRPVLR SVNSREPSQV IFCNRSPRVV
60 70 80 90 100
LPLWLNFDGE PQPYPILPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE
110 120 130 140 150
LFVPSLNVDG QPIFANITLP VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL
160 170 180
YEDLEDYPSV RKDIQRLSQE HLESQHLEEE P
Length:181
Mass (Da):20,770
Last modified:February 1, 1995 - v1
Checksum:iAE8B2E8DDD3EE987
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12570 mRNA. Translation: AAA20662.1.
S76748 mRNA. Translation: AAB33363.1.
AF513984 Genomic DNA. Translation: AAM53645.1.
BC052417 mRNA. Translation: AAH52417.2.
CCDSiCCDS20429.1.
RefSeqiNP_033533.1. NM_009507.3.
UniGeneiMm.29407.

Genome annotation databases

EnsembliENSMUST00000035673; ENSMUSP00000039418; ENSMUSG00000033933.
GeneIDi22346.
KEGGimmu:22346.
UCSCiuc009dha.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12570 mRNA. Translation: AAA20662.1.
S76748 mRNA. Translation: AAB33363.1.
AF513984 Genomic DNA. Translation: AAM53645.1.
BC052417 mRNA. Translation: AAH52417.2.
CCDSiCCDS20429.1.
RefSeqiNP_033533.1. NM_009507.3.
UniGeneiMm.29407.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HV2NMR-B123-137[»]
ProteinModelPortaliP40338.
SMRiP40338. Positions 28-170.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204518. 8 interactions.
IntActiP40338. 7 interactions.
STRINGi10090.ENSMUSP00000039418.

PTM databases

PhosphoSiteiP40338.

Proteomic databases

MaxQBiP40338.
PaxDbiP40338.
PRIDEiP40338.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035673; ENSMUSP00000039418; ENSMUSG00000033933.
GeneIDi22346.
KEGGimmu:22346.
UCSCiuc009dha.1. mouse.

Organism-specific databases

CTDi7428.
MGIiMGI:103223. Vhl.

Phylogenomic databases

eggNOGiNOG327868.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiP40338.
KOiK03871.
OMAiVGHPWMF.
OrthoDBiEOG7VMP7B.
PhylomeDBiP40338.
TreeFamiTF318985.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

NextBioi302621.
PROiP40338.
SOURCEiSearch...

Gene expression databases

BgeeiP40338.
ExpressionAtlasiP40338. baseline and differential.
GenevestigatoriP40338.

Family and domain databases

Gene3Di1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProiIPR002714. VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERiPTHR15160:SF0. PTHR15160:SF0. 1 hit.
PfamiPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMiSSF49468. SSF49468. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression of the Von Hippel-Lindau tumor suppressor gene, VHL, in human fetal kidney and during mouse embryogenesis."
    Kessler P.M., Vasavada S.P., Rackley R.R., Stackhouse T., Duh F.-M., Latif F., Lerman M.I., Zbar B., Williams B.R.
    Mol. Med. 1:457-466(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Strain: ICR.
    Tissue: Brain.
  2. "Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene."
    Gao J., Naglich J.G., Laidlaw J., Whaley J.M., Seizinger B.R., Kley N.
    Cancer Res. 55:743-747(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Human DNA blueprints protecting the VHL promoter and CpG island from methylation are functional in the mouse."
    Kuzmin I., Geil L., Schmidt L., Duh F.-M., Feigenbaum L., Nickerson M.L., Ma W., Stanbridge E.J., Zbar B., Lerman M.I.
    Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: 129/SvJ.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.

Entry informationi

Entry nameiVHL_MOUSE
AccessioniPrimary (citable) accession number: P40338
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: February 4, 2015
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.