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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 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 (By similarity).By similarity

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.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-RNO-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-RNO-8951664. Neddylation.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi3960. Vhl.

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000658111 – 185von Hippel-Lindau disease tumor suppressorAdd BLAST185

Proteomic databases

PaxDbiQ64259.
PRIDEiQ64259.

Expressioni

Gene expression databases

BgeeiENSRNOG00000010258.
GenevisibleiQ64259. RN.

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 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 (By similarity). Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB 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

GO - Molecular functioni

  • enzyme binding Source: RGD
  • protein complex binding Source: RGD
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi246987. 7 interactors.
CORUMiQ64259.
STRINGi10116.ENSRNOP00000013727.

Structurei

3D structure databases

ProteinModelPortaliQ64259.
SMRiQ64259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni123 – 132Interaction with Elongin BC complexBy similarity10

Domaini

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

Sequence similaritiesi

Belongs to the VHL family.Curated

Phylogenomic databases

eggNOGiKOG4710. Eukaryota.
ENOG4111PRU. LUCA.
GeneTreeiENSGT00390000014353.
HOGENOMiHOG000030904.
HOVERGENiHBG044781.
InParanoidiQ64259.
KOiK03871.
OMAiYWIDYQG.
OrthoDBiEOG091G0NHA.
PhylomeDBiQ64259.
TreeFamiTF318985.

Family and domain databases

CDDicd05468. pVHL. 1 hit.
Gene3Di1.10.750.10. 1 hit.
2.60.40.780. 1 hit.
InterProiView 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.
PANTHERiPTHR15160:SF1. PTHR15160:SF1. 1 hit.
PfamiView protein in Pfam
PF01847. VHL. 1 hit.
PF17211. VHL_C. 1 hit.
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.

Similar proteinsi

Entry informationi

Entry nameiVHL_RAT
AccessioniPrimary (citable) accession number: Q64259
Secondary accession number(s): Q64197, Q80WY8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: November 1, 1996
Last modified: November 22, 2017
This is version 141 of the entry and version 1 of the sequence. See 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
  2. SIMILARITY comments
    Index of protein domains and families