Literature summary for 1.14.11.7 extracted from

Homan, E.P.; Lietman, C.; Grafe, I.; Lennington, J.; Morello, R.; Napierala, D.; Jiang, M.M.; Munivez, E.M.; Dawson, B.; Bertin, T.K.; Chen, Y.; Lua, R.; Lichtarge, O.; Hicks, J.; Weis, M.A.; Eyre, D.; Lee, B.H.
Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues (2014), PLoS Genet., 10, e1004121 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene LEPRE1 or P3h1	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
D592A	site-directed mutagenesis, the mutant is able to rescue CRTAP stability	Mus musculus
H590A	site-directed mutagenesis, the mutant is able to rescue CRTAP stability. Hydroxylation status at different collagen sites in mutant mice, overview. Residue alpha1(I) K930 is 98% hydroxylated and non-glycosylated in both genotypes and alpha1(I)K87 is 92% hydroxylated in wild-type and 93% in Lepre1H662A/H662A. Collagen fibril ultrastructure, secretion rate, and steady-state levels	Mus musculus
H662A	site-directed mutagenesis, generation of mutant mice, phenotype analysis, detailed overview. The mutant is able to rescue CRTAP stability, but Lepre1H662A/H662A mice lack Pro986 collagen hydroxylation	Mus musculus
additional information	P3H1s mutants H590A, D592A, H662A, or R672A are able to restore the stability of CRTAP in cell culture	Mus musculus
R672A	site-directed mutagenesis, the mutant is able to rescue CRTAP stability	Mus musculus

General Stability

General Stability	Organism
cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1) stabilize each other in protein-protein interaction, absence of one results in degradation of the other	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
[procollagen]-L-proline + 2-oxoglutarate + O2	Mus musculus	Residue alpha1(I) K930 is 98% hydroxylated and non-glycosylated in both genotypes and alpha1(I)K87 is 92% hydroxylated in wild-type and 93% in Lepre1H662A/H662A	[procollagen]-trans-3-hydroxy-L-proline + succinate + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	Q3V1T4	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
skeletal muscle	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
[procollagen]-L-proline + 2-oxoglutarate + O2	Residue alpha1(I) K930 is 98% hydroxylated and non-glycosylated in both genotypes and alpha1(I)K87 is 92% hydroxylated in wild-type and 93% in Lepre1H662A/H662A	Mus musculus	[procollagen]-trans-3-hydroxy-L-proline + succinate + CO2	-	?

Synonyms

Synonyms	Comment	Organism
LEPRE1	-	Mus musculus
P3H1	-	Mus musculus
prolyl 3-hydroxylase 1	-	Mus musculus

General Information

General Information	Comment	Organism
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	Mus musculus
physiological function	cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1) , together with cyclophilin B, form a complex that 3-hydroxylates a single proline residue on the alpha1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other	Mus musculus

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Release 2023.1 (January 2023)