HIF

Hypoxia-inducible factors (HIFs) Antibodies

Items	Antigen/ peptide location	Antibody Host	Aff. Pure IgG or Mab (100 ug) Cat #	* Control Peptide (100 ug) Cat #
HIF-1a (Ab #1)	H, HIF-1a fusion protein	mouse, mono	HIF1A11-M
HIF-1a (Ab #2)	H, HIF-1 alpha full length protein	mouse, mono	HIF1A12-M
HIF-1a (Ab #3)	H, HIF-1a protein fragment	mouse, mono	HIF1A13-M
HIF-1b	H, HIF-1b protein	mouse, mono	HIF1B11-M	-
HIF-2a	M, 15 aa ~mid-region	Rb, poly	HIF2A11-A	HIF2A11-P

M= Mouse; R=Rat; H=Human; Rb=Rabbit; G=goat; B=Bovine, MO=Monkey; P=pig; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein. EC=extracellular; CP=cytoplasmic domains *

Hypoxia-inducible factors (HIFs) -General Information

HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis, the posttranslational modification by prolyl hydroxylation as a key regulatory event that targets HIF-alpha subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. The transcriptional complex is composed of an alpha-beta heterodimer; HIF-beta being a constitutive nuclear protein that dimerises with oxygen regulated HIF-alpha subunits. In normoxia, 4-hydroxylation of human HIF-alpha at Pro402 or Pro564 by a set of HIF prolyl hydroxylase isoenzymes (PHD 1-3) mediates HIF1-alpha recognition by von Hippel-Lindau ubiquitin ligase complex leading to its proteasomal destruction. In hypoxia (deprivation of oxygen), lack of hydroxylase activity enables HIF-alpha subunits to escape destruction and become transcriptionally active. Thus HIF hydroxylases provide a focus for understanding cellular responses to hypoxia and target for therapeutic manipulation. There are several HIF factors, which include HIF 1-alpha, HIF 1-beta, HIF 2-alpha.

HIF 1-alpha: A 812aa protein in rat and 836aa long in mouse and human (chr 14q21-14q24) Mol.wt of ~96kD. 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, 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. It is ubiquitous in expression as cytoplasmic in normoxia, nuclear translocation in response to hypoxia.

HIF 1 beta/ ARNT, a 791aa protein in rat, 800aa in mouse and 789 aa long in human (Chr. 1q21), The Cytosolic dioxin receptor, also referred to as Ah receptor, translocates to the nucleus upon binding of ligand. Ligands include dioxin and polycyclic aromatic hydrocarbons (PAH). The complex then initiates transcription of a battery of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A /HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia. It is mainly localized in nuclear region.

HIF 2-alpha/ EPAS 1, a 874aa each protein in mouse, rat and 870aa in human, The transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Expressed in most tissues, with highest levels in lung, followed by heart, kidney, brain and liver.