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Protein Page:
VHL (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
VHL 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. 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 PHF17. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains). Interacts with EPAS1. Expressed in the adult and fetal brain and kidney. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Ubiquitin ligase; Tumor suppressor
Chromosomal Location of Human Ortholog: 3p25.3
Cellular Component: nucleoplasm; intermediate filament cytoskeleton; membrane; mitochondrion; endoplasmic reticulum; nucleolus; nucleus; cytosol
Molecular Function: protein binding; enzyme binding; ubiquitin-protein ligase activity; transcription factor binding
Biological Process: negative regulation of cell proliferation; protein stabilization; regulation of transcription, DNA-dependent; positive regulation of transcription, DNA-dependent; cell morphogenesis; response to stress; protein ubiquitination; negative regulation of transcription from RNA polymerase II promoter; positive regulation of cell differentiation; proteolysis; negative regulation of apoptosis
Reference #:  P40337 (UniProtKB)
Alt. Names/Synonyms: elongin binding protein; HRCA1; Protein G7; pVHL; RCA1; VHL; VHL1; Von Hippel-Lindau disease tumor suppressor; von Hippel-Lindau tumor suppressor
Gene Symbols: VHL
Molecular weight: 24,153 Da
Basal Isoelectric point: 4.7  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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VHL

Protein Structure Not Found.


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Sites Implicated In
apoptosis, induced: S111‑p
carcinogenesis, inhibited: S111‑p
cell cycle regulation: S111‑p
cytoskeletal reorganization: S68‑p, S72‑p
transcription, altered: S33‑p, S38‑p, S43‑p
transcription, induced: S111‑p
molecular association, regulation: S68‑p, S72‑p, S111‑p
protein degradation: S33‑p, S38‑p, S43‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 S33-p EEDGGEEsGAEEsGP
1 0 S38-p EEsGAEEsGPEEsGP
1 0 S43-p EEsGPEEsGPEELGA
2 0 S68-p PVLRSVNsREPsQVI
3 0 S72-p SVNsREPsQVIFCNR
1 0 T100-p GEPQPYPtLPPGtGR
1 2 T105-p YPtLPPGtGRRIHsy
1 1 S111-p GtGRRIHsyRGHLWL
1 0 Y112-p tGRRIHsyRGHLWLF
1 0 S168-p RCLQVVRsLVkPENy
2 0 K171-sm QVVRsLVkPENyRRL
1 0 Y175-p sLVkPENyRRLDIVR
1 0 S183-p RRLDIVRsLyEDLED
0 6 Y185-p LDIVRsLyEDLEDHP
0 1 K196-ub EDHPNVQkDLERLtQ
1 0 T202-p QkDLERLtQERIAHQ
  mouse

 
- gap
- gap
- gap
S34-p PVLRSVNsREPSQVI
S38 SVNsREPSQVIFCNR
I66 GEPQPYPILPPGTGR
T71 YPILPPGTGRRIHSY
S77 GTGRRIHSYRGHLWL
Y78 TGRRIHSYRGHLWLF
S134 RCLQVVRSLVKPENY
K137 QVVRSLVKPENYRRL
Y141 SLVKPENYRRLDIVR
S149 RRLDIVRSLYEDLED
Y151 LDIVRSLYEDLEDYP
K162 EDYPSVRKDIQRLSQ
S168 RKDIQRLSQEHLESQ
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