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Protein

Von Hippel-Lindau disease tumor suppressor

Gene

Vhl

Organism
Rattus norvegicus (Rat)
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. protein complex binding Source: RGD
  2. transcription factor binding Source: RGD

GO - Biological processi

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

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Von Hippel-Lindau disease tumor suppressor
Alternative name(s):
pVHL
Gene namesi
Name:Vhl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi3960. Vhl.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Membrane By similarity; Peripheral membrane protein By similarity
  3. Nucleus By similarity

  4. Note: Colocalizes with ADRB2 at the cell membrane.By similarity

GO - Cellular componenti

  1. cilium Source: Ensembl
  2. Cul2-RING ubiquitin ligase complex Source: Ensembl
  3. cytosol Source: RGD
  4. membrane Source: UniProtKB-SubCell
  5. mitochondrion Source: RGD
  6. nucleolus Source: Ensembl
  7. nucleoplasm Source: Ensembl
  8. nucleus Source: RGD
  9. transcription factor complex Source: RGD
  10. VCB complex Source: RGD
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 – 185185Von Hippel-Lindau disease tumor suppressorPRO_0000065811Add
BLAST

Proteomic databases

PRIDEiQ64259.

Expressioni

Gene expression databases

GenevestigatoriQ64259.

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 (By similarity). Interacts with CARD9.By similarity1 Publication

Protein-protein interaction databases

BioGridi246987. 7 interactions.
STRINGi10116.ENSRNOP00000013727.

Structurei

3D structure databases

ProteinModelPortaliQ64259.
SMRiQ64259. Positions 26-175.
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.
GeneTreeiENSGT00390000014353.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiQ64259.
KOiK03871.
OMAiVGHPWMF.
OrthoDBiEOG7VMP7B.
PhylomeDBiQ64259.
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.

Q64259-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRKAASPEE AERMPGSEEI EAGRPRPVLR SVNSREPSQV IFCNRSPRVV
60 70 80 90 100
LPLWLNFDGE PQPYPTLPPG TGRRIHSYRG HLWLFRDAGT HDGLLVNQTE
110 120 130 140 150
LFVPSLNVDG QPIFANITLP VYTLKERCLQ VVRSLVKPEN YRRLDIVRSL
160 170 180
YEDLEDHPNV RKDIQRLTQE HLENQALGEE PEGVH
Length:185
Mass (Da):21,215
Last modified:November 1, 1996 - v1
Checksum:i3AD15FD9EF139E13
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14746 mRNA. Translation: AAA86874.1.
S80345 mRNA. Translation: AAB35675.1.
S81658 mRNA. Translation: AAP32238.1.
PIRiT10752.
RefSeqiNP_434688.1. NM_052801.1.
UniGeneiRn.11059.

Genome annotation databases

EnsembliENSRNOT00000013727; ENSRNOP00000013727; ENSRNOG00000010258.
GeneIDi24874.
KEGGirno:24874.
UCSCiRGD:3960. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14746 mRNA. Translation: AAA86874.1.
S80345 mRNA. Translation: AAB35675.1.
S81658 mRNA. Translation: AAP32238.1.
PIRiT10752.
RefSeqiNP_434688.1. NM_052801.1.
UniGeneiRn.11059.

3D structure databases

ProteinModelPortaliQ64259.
SMRiQ64259. Positions 26-175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246987. 7 interactions.
STRINGi10116.ENSRNOP00000013727.

Proteomic databases

PRIDEiQ64259.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000013727; ENSRNOP00000013727; ENSRNOG00000010258.
GeneIDi24874.
KEGGirno:24874.
UCSCiRGD:3960. rat.

Organism-specific databases

CTDi7428.
RGDi3960. Vhl.

Phylogenomic databases

eggNOGiNOG327868.
GeneTreeiENSGT00390000014353.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiQ64259.
KOiK03871.
OMAiVGHPWMF.
OrthoDBiEOG7VMP7B.
PhylomeDBiQ64259.
TreeFamiTF318985.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi604702.
PROiQ64259.

Gene expression databases

GenevestigatoriQ64259.

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

  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.
  4. "pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2."
    Yang H., Minamishima Y.A., Yan Q., Schlisio S., Ebert B.L., Zhang X., Zhang L., Kim W.Y., Olumi A.F., Kaelin W.G. Jr.
    Mol. Cell 28:15-27(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CARD9.

Entry informationi

Entry nameiVHL_RAT
AccessioniPrimary (citable) accession number: Q64259
Secondary accession number(s): Q64197, Q80WY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: November 1, 1996
Last modified: April 1, 2015
This is version 120 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

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways

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.