製品: PHD3 Antibody
カタログ: DF12694
タンパク質の説明: Rabbit polyclonal antibody to PHD3
アプリケーション: WB IF/ICC
反応性: Human, Mouse
予測: Pig, Bovine, Horse, Sheep, Rabbit
分子量: 28 kDa, 20 kDa; 27kD(Calculated).
ユニプロット: Q9H6Z9
RRID: AB_2845655

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:500-1:2000, IF/ICC 1:100-1:500
*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.

反応性:
Human,Mouse
予測:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(92%)
クローナリティ:
Polyclonal
特異性:
PHD3 Antibody detects endogenous levels of total PHD3.
RRID:
AB_2845655
引用形式: Affinity Biosciences Cat# DF12694, RRID:AB_2845655.
コンジュゲート:
Unconjugated.
精製:
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.
別名:

折りたたみ/展開

Egl 9 family hypoxia inducible factor 3; Egl nine homolog 3 (C. elegans); Egl nine homolog 3; Egl nine like protein 3 isoform; EGL9 homolog of C. elegans 3; EGLN3; EGLN3_HUMAN; Factor responsive smooth muscle protein; HIF Prolyl Hydroxylase 3; HIF-PH3; HIF-prolyl hydroxylase 3; HIFP4H3; HIFPH3; HPH-1; HPH-3; Hypoxia-inducible factor prolyl hydroxylase 3; P4H3; PHD3; Prolyl Hydroxylase Domain Containing Protein 3; Prolyl hydroxylase domain-containing protein 3; SM20;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
Q9H6Z9 EGLN3_HUMAN:

Widely expressed at low levels. Expressed at higher levels in adult heart (cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle), lung and placenta, and in fetal spleen, heart and skeletal muscle. Also expressed in pancreas. Localized to pancreatic acini and islet cells.

タンパク質配列:
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED

種類予測

種類予測:

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
Horse
100
Bovine
100
Sheep
100
Rabbit
92
Xenopus
75
Chicken
75
Dog
0
Zebrafish
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - Q9H6Z9 基板として

Site PTM Type Enzyme
K48 Ubiquitination
T130 Phosphorylation
K159 Ubiquitination
K172 Ubiquitination
Y206 Phosphorylation
T209 Phosphorylation
Y212 Phosphorylation

研究背景

機能:

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif.

細胞の位置付け:

Nucleus. Cytoplasm.
Note: Colocalizes with WDR83 in the cytoplasm.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Widely expressed at low levels. Expressed at higher levels in adult heart (cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle), lung and placenta, and in fetal spleen, heart and skeletal muscle. Also expressed in pancreas. Localized to pancreatic acini and islet cells.

サブユニット構造:

Interacts with WDR83; the interaction leads to almost complete elimination of HIF-mediated reporter activity (By similarity). Interacts with BCL2 (via its BH4 domain); the interaction disrupts the BAX-BCL4 complex inhibiting the anti-apoptotic activity of BCL2. Interacts with ADRB2; the interaction hydroxylates ADRB2 facilitating its ubiquitination by the VHL-E3 ligase complex. Interacts with PAX2; the interaction targets PAX2 for destruction. Interacts with PKM; the interaction hydroxylates PKM in hypoxia.

タンパク質ファミリー:

The Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.

研究領域

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

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

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

参考文献

1). ETV2 regulating PHD2-HIF-1α axis controls metabolism reprogramming promotes vascularized bone regeneration. Bioactive Materials, 2024 [IF=18.9]

Application: WB    Species: Mouse    Sample:

Fig. 2. ETV2 induces HIF-1α stabilization and nuclear accumulation by transcriptional inhibition of PHD2 and ERK1/2 phosphorylation (A) KEGG functional enrichment analysis of RNA sequence (B) A heatmap displays genes associated with osteogenesis and HIF-1 signaling (C, D) The protein and mRNA expression of HIF-1α and PHDs following ETV2 overexpression (E) Schematic of putative ETV2 binding elements on PHD2 promoter region (F) Dual luciferase reporter gene assay of ETV2 and PHD2 (G) Cytoplasmic HIF-1α, total and phosphorylated ERK1/2, and intracellular HIF-1α expression post ETV2 overexpression (H) Representative immunofluorescent images of intracellular phosphorylated ERK1/2. The Cy3 channel fluorescence represents lentiviral transfection. Scale bar: 50 μm (I) Representative immunofluorescent images of intranuclear HIF-1α. The Cy3 channel fluorescence represents lentiviral transfection. The orange arrows indicate the fluorescence of HIF-1α in the nucleus, while the white arrows point to the absence of HIF-1α fluorescence in the nucleus. Scale bar: 50 μm (NS, no significant difference, NC, negative control; OE, overexpression. Data are presented as the mean of >3 independent experiments ±SD. *P < 0.05, **P < 0.01, and ***P < 0.001).

2). Systems pharmacology reveals the mechanism of Astragaloside IV in improving immune activity on cyclophosphamide-induced immunosuppressed mice. Journal of Ethnopharmacology, 2023 [IF=5.4]

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