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P40338 (VHL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
pVHL
Gene names
Name:Vhl
Synonyms:Vhlh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length181 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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.

Subcellular location

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

Developmental stage

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. Ref.1

Domain

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

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Membrane
Nucleus
   DiseaseTumor suppressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from mutant phenotype PubMed 16537898. Source: MGI

blood vessel endothelial cell migration

Inferred from mutant phenotype PubMed 16537898. Source: MGI

extracellular matrix organization

Inferred from mutant phenotype PubMed 16537898. Source: MGI

negative regulation of thymocyte apoptotic process

Inferred from mutant phenotype PubMed 15456877. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

proteasomal protein catabolic process

Inferred from mutant phenotype PubMed 17981124. Source: MGI

protein catabolic process

Inferred from mutant phenotype PubMed 12832481. Source: MGI

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of apoptotic signaling pathway

Inferred from genetic interaction PubMed 15456877. Source: MGI

regulation of catecholamine metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of thymocyte apoptotic process

Inferred from genetic interaction PubMed 15456877. Source: MGI

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentVCB complex

Inferred from electronic annotation. Source: Ensembl

cilium

Inferred from direct assay PubMed 17825299. Source: MGI

cytosol

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 15601820. Source: MGI

protein complex binding

Inferred from direct assay PubMed 17825299. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 181181Von Hippel-Lindau disease tumor suppressor
PRO_0000065810

Regions

Region123 – 13210Interaction with Elongin BC complex By similarity

Secondary structure

... 181
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P40338 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: AE8B2E8DDD3EE987

FASTA18120,770
        10         20         30         40         50         60 
MPRKAASPEE AAGEPGPEEM EAGRPRPVLR SVNSREPSQV IFCNRSPRVV LPLWLNFDGE 

        70         80         90        100        110        120 
PQPYPILPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE LFVPSLNVDG QPIFANITLP 

       130        140        150        160        170        180 
VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL YEDLEDYPSV RKDIQRLSQE HLESQHLEEE 


P 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U12570 mRNA. Translation: AAA20662.1.
S76748 mRNA. Translation: AAB33363.1.
AF513984 Genomic DNA. Translation: AAM53645.1.
BC052417 mRNA. Translation: AAH52417.2.
CCDSCCDS20429.1.
RefSeqNP_033533.1. NM_009507.3.
UniGeneMm.29407.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HV2NMR-B123-137[»]
ProteinModelPortalP40338.
SMRP40338. Positions 28-170.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204518. 8 interactions.
IntActP40338. 7 interactions.
STRING10090.ENSMUSP00000039418.

PTM databases

PhosphoSiteP40338.

Proteomic databases

PaxDbP40338.
PRIDEP40338.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035673; ENSMUSP00000039418; ENSMUSG00000033933.
GeneID22346.
KEGGmmu:22346.
UCSCuc009dha.1. mouse.

Organism-specific databases

CTD7428.
MGIMGI:103223. Vhl.

Phylogenomic databases

eggNOGNOG327868.
HOGENOMHOG000030904.
HOVERGENHBG044781.
InParanoidP40338.
KOK03871.
OMANTREPSQ.
OrthoDBEOG7VMP7B.
PhylomeDBP40338.
TreeFamTF318985.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressP40338.
BgeeP40338.
GenevestigatorP40338.

Family and domain databases

Gene3D1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProIPR002714. Tumour_suppress_VHL.
IPR024048. VHL_alpha_dom.
IPR024053. VHL_beta_dom.
IPR022772. VHL_tumour_suppress_b/a_dom.
[Graphical view]
PANTHERPTHR15160:SF0. PTHR15160:SF0. 1 hit.
PfamPF01847. VHL. 1 hit.
[Graphical view]
SUPFAMSSF49468. SSF49468. 1 hit.
ProtoNetSearch...

Other

NextBio302621.
PROP40338.
SOURCESearch...

Entry information

Entry nameVHL_MOUSE
AccessionPrimary (citable) accession number: P40338
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot