产品: VHL 抗体
货号: DF6104
描述: Rabbit polyclonal antibody to VHL
应用: WB IHC
反应: Human, Mouse, Rat
预测: Pig, Bovine, Dog
分子量: 24kDa; 24kD(Calculated).
蛋白号: P40337
RRID: AB_2838072

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产品描述

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

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(100%), Bovine(88%), Dog(88%)
克隆:
Polyclonal
特异性:
VHL Antibody detects endogenous levels of total VHL.
RRID:
AB_2838072
引用格式: Affinity Biosciences Cat# DF6104, RRID:AB_2838072.
偶联:
Unconjugated.
纯化:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
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.
别名:

展开/折叠

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;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
P40337 VHL_HUMAN:

Expressed in the adult and fetal brain and kidney.

描述:
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.
序列:
MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

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

翻译修饰 - P40337 作为底物

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)

研究背景

功能:

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.

细胞定位:

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
组织特异性:

Expressed in the adult and fetal brain and kidney.

亚基结构:

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.

蛋白家族:

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.

研究领域

· 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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