hypoxic

Unlike some other CBS-domain containing proteins does not seem to bind AMP.

Abstract Interleukin-11 (IL-11) is a pleiotropic cytokine that belongs to gp130 family. IL-11 and its receptor, IL-11Ra, are expressed in human cancers,human cancer cells expressed a functional IL-11Ra subunit, which triggered signal transduction either by exogenous recombinant human IL-11 or by autocrine production of IL-11 in cells cultured under hypoxic conditions. IL-11 Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 20.48 kDa and the accession number is P20808.

Myoglobin(MB) is a cytoplasmic protein expressed in myocytes of the heart and skeletal muscle that reversibly binds oxygen. It belongs to the globin family. Functions of myoglobin include oxygen storage and transport, as well as scavenging of NO and reactive oxygen species. MB serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Myoglobin also serves as a sensitive marker for muscle injury resulting from cardiac infarction. Surprisingly, mice in which myoglobin has been removed by gene targeting are able to perform extensive exercise and respond normally to hypoxic challenge.

CA9 is a member of the carbonic anhydrases' family, that is often expressed in cancer cells under hypoxic condition. CA9 expression potentially contributes to the regulation of cancer cell differentiation and mediates tumour-associated genes and signalling pathways, including apoptosis, hypoxia, G2M checkpoint, PI3K AKR mTOR signalling and TGF-beta signalling pathways. CA9 Carbonic Anhydrase IX Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 41.03 kDa and the accession number is A0A2K5VQG9.

CA9 is a member of the carbonic anhydrases' family, that is often expressed in cancer cells under hypoxic condition. CA9 expression potentially contributes to the regulation of cancer cell differentiation and mediates tumour-associated genes and signalling pathways, including apoptosis, hypoxia, G2M checkpoint, PI3K AKR mTOR signalling and TGF-beta signalling pathways. CA9 Carbonic Anhydrase IX Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 43.7 kDa and the accession number is Q16790.

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 HIF1B. 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. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.

Fructose-2,6-biphosphatase 3, also known as 6-phosphofructo-2-kinase or PFK2 or PFKFB3, involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls the activity of the enzymes phosphofructokinase 1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1) to regulate glycolysis and gluconeogenesis. Highly phosphorylated PFKFB3 protein was found in human tumor cells, vascular endothelial cells, and smooth muscle cells. Because of its proto-oncogenic character, the PFK-2 FBPase-2 of the PFKFB3 gene is assumed to play a critical role in tumorigenesis. PFKFB3 also plays a crucial role in the progression of cancerous cells by enabling their glycolytic pathways even under severe hypoxic conditions, which makes it a potential target for cancer therapy.

HIF-1 alpha, also known as HIF1A, contains 1 basic helix-loop-helix (bHLH) domain, 1 PAC (PAS-associated C-terminal) domain, and 2 PAS (PER-ARNT-SIM) domains. It is one of the two subunits of Hypoxia-inducible factor-1 (HIF1). 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). HIF-1 alpha is expressed in most tissues with the highest levels in the kidney and heart. It is 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. HIF-1 alpha functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, it 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. HIF1A plays an essential role in embryonic vascularization, tumor angiogenesis, and the pathophysiology of ischemic disease. HIF-1 alpha binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires the recruitment of transcriptional coactivators such as CREBPB and EP300.

Abstract Interleukin-11 (IL-11) is a pleiotropic cytokine that belongs to gp130 family. IL-11 and its receptor, IL-11Ra, are expressed in human cancers,human cancer cells expressed a functional IL-11Ra subunit, which triggered signal transduction either by exogenous recombinant human IL-11 or by autocrine production of IL-11 in cells cultured under hypoxic conditions. IL-11 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 20.24 kDa and the accession number is P20809-1.

Mitogen-activated protein kinase 8 (MAPK8), also known as JNK1, is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. The protein kinases JNK1 has been found to serve as critical molecular links between obesity, metabolic inflammation, and disorders of glucose homeostasis. It is critically involved in the promotion of diet-induced obesity, metabolic inflammation, and beta-cell dysfunction. The selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. Genetic analysis indicates that the effects of JNK1 can be separated from the effects of JNK1 on obesity. JNK1 is a potential pharmacological target for the development of drugs that might be useful for the treatment of metabolic syndrome, and type 2 diabetes. Furthermore, JNK1 plays a major role in hypoxic cellular damage. JNK1 protein might be an attractive target for anti-hypoxic therapy in increasing resistance to many pathological conditions and diseases, leading to the oxygen deficit.

MAPK14 contains 1 protein kinase domain and belongs to the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. MAPK14 can be detected in the brain, heart, placenta, pancreas, and skeletal muscle and it is expressed to a lesser extent in the lung, liver, and kidney. MAPK14 is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1 TAB1 protein with MAPK14. The substrates of p38 alpha include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of p38 alpha in stress-related transcription and cell cycle regulation, as well as in genotoxic stress response. In response to activation by environmental stress, pro-inflammatory cytokines, and lipopolysaccharide, MAPK14 phosphorylates some transcription factors, such as ELK1 and ATF2, and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. MAPK14 plays a critical role in the production of some cytokines, for example, IL-6. It may play a role in the stabilization of EPO mRNA during hypoxic stress. Isoform Mxi2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2.

Fructose-2,6-biphosphatase 3, also known as 6-phosphofructo-2-kinase or PFK2 or PFKFB3, is a potent activator of phosphofructokinase, which is a rate-limiting enzyme of glycolysis. Highly phosphorylated PFKFB3 protein was found in human tumor cells, vascular endothelial cells, and smooth muscle cells. Fructose 2,6-bisphosphate (Fru-2,6-BP) is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), a rate-limiting enzyme and essential control point in glycolysis. The concentration of PFK2 depends on the activity of the bifunctional enzyme, 6-phosphofructo-2-kinase fructose-2,6-bisphosphatase (PFK-2 FBPase). PFK2 controls the glycolytic flux via the allosteric activator fructose 2,6-bisphosphate. Because of its proto-oncogenic character, the PFK-2 FBPase-2 of the PFKFB3 gene is assumed to play a critical role in tumorigenesis. The hypoxia-inducible form of 6-phosphofructo-2-kinase fructose-2,6-bisphosphatase (PFKFB3) plays a crucial role in the progression of cancerous cells by enabling their glycolytic pathways even under severely hypoxic conditions.