VHL Antibody - #DF6104

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Product: VHL Antibody
Catalog: DF6104
Description: Rabbit polyclonal antibody to VHL
Application: WB IHC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Dog
Mol.Wt.: 24kDa; 24kD(Calculated).
Uniprot: P40337
RRID: AB_2838072

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Related Downloads
MS Report
HPLC Report
MSDS
Data Sheet
COA
Protocols
WB Handbook
IHC Protocol
IF/ICC Protocol

Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(100%), Bovine(88%), Dog(88%)
Clonality:
Polyclonal
Specificity:
VHL Antibody detects endogenous levels of total VHL.
RRID:
AB_2838072
Cite Format: Affinity Biosciences Cat# DF6104, RRID:AB_2838072.
Conjugate:
Unconjugated.
Purification:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

Elongin binding protein; G7 protein; HRCA 1; HRCA1; Protein G7; pVHL; RCA 1; RCA1; VHL 1; VHL; VHL_HUMAN; VHL1; VHLH; Von Hippel Lindau disease tumor suppressor; von Hippel Lindau syndrome; von Hippel Lindau tumor suppressor; Von Hippel Lindau tumor suppressor, E3 ubiquitin protein ligase; Von Hippel-Lindau disease tumor suppressor;

Immunogens

Immunogen:
Uniprot:

P40337(VHL_HUMAN) >>Visit HPA database.

Gene(ID):
VHL(7428)
Expression:
P40337 VHL_HUMAN:

Expressed in the adult and fetal brain and kidney.

Description:
The Von Hippel-Lindau (VHL) protein is a substrate recognition component of an E3 ubiquitin ligase complex containing elongin BC (TCEB1 and TCEB2), cullin 1 (CUL1), and RING-box protein 1 (RBX1) (1,2,3). VHL protein has been shown to exist as three distinct isoforms resulting from alternatively spliced transcript variants (4). Loss of VHL protein function results in a dominantly inherited familial cancer syndrome that manifests as angiomas of the retina, hemangioblastomas of the central nervous system, renal clear-cell carcinomas and pheochromocytomas (4). Under normoxic conditions, VHL directs the ubiquitylation and subsequent proteosomal degradation of the hypoxia inducible factor HIF alpha, maintaining very low levels of HIF alpha in the cell. Cellular exposure to hypoxic conditions, or loss of VHL protein function, results in increased HIF alpha protein levels and increased expression of HIF-induced gene products, many of which are angiogenesis factors such as vascular endothelial growth factor (VEGF). Thus, loss of VHL protein function is believed to contribute to the formation of highly vascular neoplasias (4). In addition to HIF alpha, VHL is known to regulate the ubiquitylation of several other proteins, including tat-binding protein 1 (TBP-1), the atypical protein kinase C lambda (aPKC), and two subunits of the multiprotein RNA Polymerase II complex (RPB1 and RPB7) (5,6,7,8). Interactions with elongin BC, RPB1, RPB7 and the pVHL-associated KRAB-A domain containing protein (VHLaK) suggest that VHL may also play a more direct role in transcriptional repression.
Sequence:
MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Bovine
88
Dog
88
Horse
0
Sheep
0
Xenopus
0
Zebrafish
0
Chicken
0
Rabbit
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P40337 As Substrate

Site PTM Type Enzyme
S33 Phosphorylation P68400 (CSNK2A1)
S38 Phosphorylation P68400 (CSNK2A1)
S43 Phosphorylation P68400 (CSNK2A1)
S68 Phosphorylation P49841 (GSK3B)
S72 Phosphorylation O14965 (AURKA) , P48729 (CSNK1A1)
R79 Methylation
S80 Phosphorylation
T100 Phosphorylation Q96PY6 (NEK1)
T105 Phosphorylation Q96PY6 (NEK1)
S111 Phosphorylation O96017 (CHEK2)
Y112 Phosphorylation Q96PY6 (NEK1)
K159 Ubiquitination
S168 Phosphorylation Q96PY6 (NEK1)
K171 Sumoylation
K171 Ubiquitination
Y175 Phosphorylation Q96PY6 (NEK1)
S183 Phosphorylation Q96PY6 (NEK1)
Y185 Phosphorylation
K196 Ubiquitination
T202 Phosphorylation Q96PY6 (NEK1)

Research Backgrounds

Function:

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.

Subcellular Location:

Cytoplasm. Membrane>Peripheral membrane protein. Nucleus.
Note: Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.

Cytoplasm. Nucleus.
Note: Equally distributed between the nucleus and the cytoplasm but not membrane-associated.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Expressed in the adult and fetal brain and kidney.

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 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. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB 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. Interacts with CARD9.

Family&Domains:

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

Belongs to the VHL family.

Research Fields

· Environmental Information Processing > Signal transduction > HIF-1 signaling pathway.   (View pathway)

· Genetic Information Processing > Folding, sorting and degradation > Ubiquitin mediated proteolysis.   (View pathway)

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Renal cell carcinoma.   (View pathway)

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