EC Number   |
General Information |
Reference |
|---|
   1.14.11.7 | drug target |
the enzyme could be considered as a potential target for anti-angiogenesis therapy |
764921 |
| 1.14.11.7 | malfunction |
a knockdown of P3H2 protein using RNA interference reduces 3-hydroxylation at Pro-944, Pro-707, and the GPP repeat at the C-terminus of the triple helix but not at Pro-986 of the clade A pNalpha1(II) collagen chain. When P3H2 expression is turned off, 3-hydroxylation at residue Pro-944 in the alpha2(V) chain is lost, and 3Hyp occupancy at Pro-707 in alpha2(V) and alpha2(I) chains is significantly reduced |
727884 |
| 1.14.11.7 | malfunction |
epigenetic inactivation of the enzyme in human cancer |
697017 |
| 1.14.11.7 | malfunction |
in case of enzyme defects, 3-hydroxylation of the Pro986 residue is absent or severly reduced. Defects in the genes encoding cartilage-associated protein, CRTAP, or prolyl 3-hydroxylase 1, P3H1/LEPRE1, cause the classical osteogenesis imperfecta, OI, a dominant genetic disorder of connective tissue, overview. Patients with mutations in CRTAP or LEPRE1 have a lethal to severe osteochondrodystrophy that overlaps with Sillence types II and III classical osteogenesis imperfecta but has distinctive features |
697192 |
| 1.14.11.7 | malfunction |
loss-of function studies show that PHD3 serves as a co-activator of NF-kappaB signaling activity in NP cells. PHD3 interacts with, and co-localizes with, p65 |
727931 |
| 1.14.11.7 | malfunction |
mutations in LEPREL1, the gene encoding prolyl 3-hydroxylase-2 (P3H2), cause severe nonsyndromic myopia. Collagens I and IV from P3h2-null mouse eye tissues are significantly reduced in 3-hydroxylation compared with wild-type littermates. Loss of P3h2 causes altered collagen prolyl 3-hydroxylation from multiple tissues, e.g. leading to structural abnormalities in multiple eye tissues, but particularly sclera, causing progressive myopia. Phenotype, overview |
745337 |
| 1.14.11.7 | malfunction |
mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (LEPRE1) are the causes of recessive osteogenesis imperfecta. The absence of the post-translational modification, 3-hydroxylation of Pro986of collagen, may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. absence of one results in degradation of the other. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. Generated mutant mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1H662A) show abolished P3h1 activity but retain ability to form a complex with Crtap and thus the collagen chaperone function. The mutant mice show absence of prolyl 3-hydroxylation at Pro986 of the alpha1(I) and alpha1(II) collagen chains but no significant over-modification at other collagen residues. They are normal in appearance, have no growth defects and normal cartilage growth plate histology but show decreased trabecular bone mass. This mouse model recapitulates elements of the bone phenotype of osteogenesis imperfecta but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity versus complete ablation of the prolyl 3-hydroxylation complex |
746168 |
| 1.14.11.7 | malfunction |
null mutation of the prolyl 3-hydroxylase 1, P3H1/LEPRE1, gene cause OI type VIII, a recessive form of osteogenesis imperfecta with severe to lethal bone dysplasia and overmodification of the type I collagen helical region, overview |
698181 |
| 1.14.11.7 | malfunction |
P3H2-null mice are embryonic-lethal by embryonic day 8.5. The mechanism of the unexpectedly early lethality involves the interaction of non-3-hydroxylated embryonic type IV collagen with the maternal platelet-specific glycoprotein VI (GPVI). This interaction results in maternal platelet aggregation, thrombosis of the maternal blood, and death of the embryo. The phenotype is completely rescued by producing double knockouts of P3H2 and GPVI. Double nulls are viable and fertile. Epigenetic silencing of P3H2 in breast cancers implies that the interaction between GPVI and nonΒ3-hydroxylated type IV collagen might also play a role in the progression of malignant tumors and metastasis |
746295 |
| 1.14.11.7 | malfunction |
PHD3-/- mice have lower cerebral blood flow after reperfusion than wild-type littermates but comparable functional outcomes, suggesting that deleterious haemodynamic effects are counteracted by alternative neuroprotective benefits in this circumstance |
728198 |
