background:
PHD1 catalyzes the posttranslational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins and hydroxylates HIF-1 alpha at Pro-402 and Pro-564, and HIF-2 alpha. It functions as a cellular oxygen sensor and, under normoxic conditions, targets HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitylation complex. It may play a role in cell growth regulation.
Function:
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 SLCterminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. [CATALYTIC ACTIVITY] Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO(2).
Subunit:
Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIFs. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Interacts with EPAS1.
Subcellular Location:
Cytoplasm. Nucleus.
Tissue Specificity:
According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.
Similarity:
Contains 1 Fe2OG dioxygenase domain.
Contains 1 MYND-type zinc finger.
Database links:
Entrez Gene: 112398 Human
Entrez Gene: 11486 Mouse
Entrez Gene: 308457 Rat
Omim: 606424 Human
SwissProt: Q96KS0 Human
SwissProt: Q91YE2 Mouse
SwissProt: Q6AYU4 Rat
Unigene: 515417 Human
Unigene: 29978 Mouse
Unigene: 43384 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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