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Q64259 (VHL_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length185 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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 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.

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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: Ensembl

blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of thymocyte apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 11912140. Source: RGD

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from direct assay PubMed 20125055. Source: RGD

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

proteasomal protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein heterooligomerization

Inferred from physical interaction PubMed 9122164. Source: RGD

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of catecholamine metabolic process

Inferred from mutant phenotype PubMed 11912140. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 15507234. Source: RGD

response to hypoxia

Inferred from mutant phenotype PubMed 11912140. Source: RGD

   Cellular_componentVCB complex

Inferred from direct assay PubMed 10213691PubMed 9122164. Source: RGD

cytosol

Inferred from direct assay Ref.1. Source: RGD

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay PubMed 10850420. Source: RGD

nucleus

Inferred from direct assay Ref.1. Source: RGD

transcription factor complex

Traceable author statement PubMed 1966765. Source: RGD

   Molecular_functiontranscription factor binding

Traceable author statement PubMed 1966765. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 185185Von Hippel-Lindau disease tumor suppressor
PRO_0000065811

Regions

Region123 – 13210Interaction with Elongin BC complex By similarity

Sequences

Sequence LengthMass (Da)Tools
Q64259 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 3AD15FD9EF139E13

FASTA18521,215
        10         20         30         40         50         60 
MPRKAASPEE AERMPGSEEI EAGRPRPVLR SVNSREPSQV IFCNRSPRVV LPLWLNFDGE 

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

       130        140        150        160        170        180 
VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL YEDLEDHPNV RKDIQRLTQE HLENQALGEE 


PEGVH 

« Hide

References

[1]"Characterization of the VHL tumor suppressor gene product: localization, complex formation, and the effect of natural inactivating mutations."
Duan D.R., Humphrey J.S., Chen D.Y., Weng Y., Sukegawa J., Lee S., Gnarra J.R., Linehan W.M., Klausner R.D.
Proc. Natl. Acad. Sci. U.S.A. 92:6459-6463(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning of the rat homologue of the von Hippel-Lindau tumor suppressor gene and its non-somatic mutation in rat renal cell carcinomas."
Kikuchi Y., Kobayashi E., Nishizawa M., Hamazaki S., Okada S., Hino O.
Jpn. J. Cancer Res. 86:905-909(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus."
Walker C., Ahn Y.T., Everitt J., Yuan X.
Mol. Carcinog. 15:154-161(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-153.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U14746 mRNA. Translation: AAA86874.1.
S80345 mRNA. Translation: AAB35675.1.
S81658 mRNA. Translation: AAP32238.1.
PIRT10752.
RefSeqNP_434688.1. NM_052801.1.
UniGeneRn.11059.

3D structure databases

ProteinModelPortalQ64259.
SMRQ64259. Positions 26-175.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246987. 7 interactions.
STRING10116.ENSRNOP00000013727.

Proteomic databases

PRIDEQ64259.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000013727; ENSRNOP00000013727; ENSRNOG00000010258.
GeneID24874.
KEGGrno:24874.
UCSCRGD:3960. rat.

Organism-specific databases

CTD7428.
RGD3960. Vhl.

Phylogenomic databases

eggNOGNOG327868.
GeneTreeENSGT00390000014353.
HOGENOMHOG000030904.
HOVERGENHBG044781.
InParanoidQ64259.
KOK03871.
OMANTREPSQ.
OrthoDBEOG7VMP7B.
TreeFamTF318985.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

GenevestigatorQ64259.

Family and domain databases

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

Other

NextBio604702.
PROQ64259.

Entry information

Entry nameVHL_RAT
AccessionPrimary (citable) accession number: Q64259
Secondary accession number(s): Q64197, Q80WY8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: November 1, 1996
Last modified: February 19, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways