产品描述

来源:
Mouse
应用:
ELISA 1:10000, WB 1:500-1:2000, IHC 1:200-1:1000, IF/ICC 1:200-1:1000
*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,Monkey
克隆:
Monoclonal [AFB1879]
特异性:
HIF1A antibody detects endogenous levels of total HIF1A.
RRID:
AB_2833903
引用格式: Affinity Biosciences Cat# BF0593, RRID:AB_2833903.
偶联:
Unconjugated.
纯化:
Affinity-chromatography.
保存:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), 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

ARNT interacting protein; ARNT-interacting protein; Basic helix loop helix PAS protein MOP1; Basic-helix-loop-helix-PAS protein MOP1; bHLHe78; Class E basic helix-loop-helix protein 78; HIF 1A; HIF 1alpha; HIF-1-alpha; HIF1 A; HIF1 Alpha; HIF1; HIF1-alpha; HIF1A; HIF1A_HUMAN; Hypoxia inducible factor 1 alpha; Hypoxia inducible factor 1 alpha isoform I.3; Hypoxia inducible factor 1 alpha subunit; Hypoxia inducible factor 1 alpha subunit basic helix loop helix transcription factor; Hypoxia inducible factor 1, alpha subunit (basic helix loop helix transcription factor); Hypoxia inducible factor1alpha; Hypoxia-inducible factor 1-alpha; Member of PAS protein 1; Member of PAS superfamily 1; Member of the PAS Superfamily 1; MOP 1; MOP1; PAS domain-containing protein 8; PASD 8; PASD8;

抗原和靶标

免疫原:

Purified recombinant fragment of human HIF1A expressed in E. Coli.

Uniprot:
基因/基因ID:
表达:
Q16665 HIF1A_HUMAN:

Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland.

描述:
Hypoxia-inducible factor-1 (HIF1) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF1 is a heterodimer composed of an alpha subunit and a beta subunit. The beta subunit has been identified as the aryl hydrocarbon receptor nuclear translocator (ARNT). This gene encodes the alpha subunit of HIF-1. Overexpression of a natural antisense transcript (aHIF) of this gene has been shown to be associated with nonpapillary renal carcinomas. Two alternative transcripts encoding different isoforms have been identified. (provided by RefSeq) Tissue specificity: Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors.
序列:
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLFAEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKRKMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN

翻译修饰 - Q16665 作为底物

Site PTM Type Enzyme
K10 Acetylation
K10 Sumoylation
K11 Acetylation
K12 Acetylation
K19 Acetylation
K21 Acetylation
S31 Phosphorylation
K32 Ubiquitination
T63 Phosphorylation
Y66 Phosphorylation
K71 Ubiquitination
K85 Ubiquitination
S113 Phosphorylation
K172 Ubiquitination
K185 Sumoylation
K185 Ubiquitination
S247 Phosphorylation P48730 (CSNK1D)
K251 Ubiquitination
Y276 Phosphorylation
K289 Ubiquitination
K297 Ubiquitination
K377 Ubiquitination
K389 Acetylation
K389 Ubiquitination
K391 Methylation
K391 Sumoylation
K391 Ubiquitination
S451 Phosphorylation
T455 Phosphorylation
T458 Phosphorylation
K460 Ubiquitination
S465 Phosphorylation
K477 Sumoylation
K477 Ubiquitination
C520 S-Nitrosylation
K532 Acetylation
K532 Ubiquitination
K538 Ubiquitination
K547 Ubiquitination
S551 Phosphorylation
T555 Phosphorylation
Y565 Phosphorylation
S576 Phosphorylation Q9H4B4 (PLK3)
S589 Phosphorylation
K636 Ubiquitination
S641 Phosphorylation P28482 (MAPK1) , P27361 (MAPK3)
S643 Phosphorylation P28482 (MAPK1) , P27361 (MAPK3)
K649 Ubiquitination
T651 Phosphorylation
T652 Phosphorylation
S653 Phosphorylation
S656 Phosphorylation
S657 Phosphorylation Q9H4B4 (PLK3)
S668 Phosphorylation P06493 (CDK1)
K674 Acetylation
K674 Ubiquitination
K682 Ubiquitination
S683 Phosphorylation
S687 Phosphorylation
S692 Phosphorylation
S696 Phosphorylation Q13315 (ATM)
T700 Phosphorylation
K709 Acetylation
K709 Ubiquitination
K721 Ubiquitination
S727 Phosphorylation
S760 Phosphorylation
S761 Phosphorylation
K769 Ubiquitination
T796 Phosphorylation
S797 Phosphorylation Q5S007 (LRRK2)
C800 S-Nitrosylation
S809 Phosphorylation

研究背景

功能:

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.

翻译修饰:

S-nitrosylation of Cys-800 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.

Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding. Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome.

Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia. Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation. Desumoylation by SENP1 increases its stability amd transcriptional activity. There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity.

Acetylation of Lys-532 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylation of Lys-709 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation.

Polyubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-532 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-803. Ubiquitinated by a CUL2-based E3 ligase.

In normoxia, is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-564. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization. In normoxia, is hydroxylated on Asn-803 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. This hydroxylation is inhibited by the Cu/Zn-chelator, Clioquinol. Repressed by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation.

The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.

细胞定位:

Cytoplasm. Nucleus. Nucleus speckle.
Note: Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to hypoxia (PubMed:9822602).

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 most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland.

亚基结构:

Interacts with the ARNT; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability (By similarity). Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10 (By similarity). Interacts with HIF3A (By similarity). Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation. Interacts (via N-terminus) with USP19. Interacts with SIRT2. Interacts (deacetylated form) with EGLN1. Interacts with CBFA2T3. Interacts with HSP90AA1 and HSP90AB1.

蛋白家族:

Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID).

研究领域

· Cellular Processes > Transport and catabolism > Autophagy - animal.   (View pathway)

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

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

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

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

· Human Diseases > Cancers: Overview > Central carbon metabolism in cancer.   (View pathway)

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

· Organismal Systems > Immune system > Th17 cell differentiation.   (View pathway)

· Organismal Systems > Endocrine system > Thyroid hormone signaling pathway.   (View pathway)

文献引用

1). Alleviated NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in lipopolysaccharide-induced inflammation under hypoxia. Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2024 (PubMed: 38189810) [IF=6.7]

2). Lack of MOF decreases susceptibility to hypoxia and promotes multidrug resistance in hepatocellular carcinoma via HIF-1α. Frontiers in Cell and Developmental Biology, 2021 (PubMed: 34540836) [IF=5.5]

Application: WB    Species: Human    Sample: HCC tissues

FIGURE 1 MOF expression is negatively correlated with HIF-1α expression in HCC tissues and in response to hypoxia. (A) Representative western blots of MOF and HIF-1α in HCC tissues (T) and their paired peritumoral tissues (P). (B) IHC staining images of representative HCC tissues with antibodies against human MOF and HIF-1α, and (C) statistical relationship between MOF and HIF-1α scores in HCC. Chi-square values: 0–3, 10.49, df = 3; 1–3, 8.574, df = 3; 2–3, 4.875, df = 3. Scale bar: 100 μm (left in #1 and #2), 50 μm (right in #1 and #2). (D,E) Western blots of MOF and HIF-1α in Huh-7 (upper panel) and Hep3B (lower panel) cells upon exposure to increasing concentrations of CoCl2-mimicked hypoxia for 24 h (D), or to 100 μM CoCl2 over a time course (E). ∗P < 0.05; n.s., not significant.

3). HIF‐1α interacts with Kindlin‐2 and influences breast cancer elasticity: A study based on shear wave elastography imaging. Cancer Medicine, 2020 (PubMed: 32436609) [IF=4.0]

Application: WB    Species: human    Sample: breast cell

FIGURE 3| HIF-1α interacts with Kindlin-2 and influences collagen biogenesis by targeting P4HA1 and FAK. (A-C) HIF-1α was overexpressed with HIF-1α plasmid or knocked down with HIF-1α siRNA (A), HIF-1α mRNA expression level was analyzed by real-time PCR (B), cell lysates were analyzed by western blot with the indicated antibodies. The expression levels of Kindlin-2, p-FAK, and P4HA1 were consistent with HIF-1α expression (C).

4). Xiaoyu Xiezhuo Drink Protects against Ischemia-Reperfusion Acute Kidney Injury in Aged Mice through Inhibiting the TGF-β1/Smad3 and HIF1 Signaling Pathways. BioMed Research International, 2021 (PubMed: 34545331)

Application: WB    Species: Mice    Sample: kidney tissues

Figure 10 Effect of XXD on the TGF-β1/Smad3 and HIF1 signaling pathways of kidney tissues in AKI mice. (a) Representative western blots for MMP-9, α-SMA, ICAM-1, TGF-β1, Smad7, HIF1A, and GAPDH. Quantitative analysis of (b) MMP-9, α-SMA, ICAM-1, TGF-β1, Smad7, and HIF1A and normalized with GAPDH. (c) Representative protein bands of p-Smad3, Smad3, and β-actin in XXD-treated AKI mice. (d) Quantitative analysis of p-Smad3 and Smad3 and normalized with β-actin. All data are represented as the mean ± SD (n = 3). ▲P < 0.05, ▲▲P < 0.01 vs. the model group.

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