PMID:15044469

Citation	Vranka, JA, Sakai, LY and Bächinger, HP (2004) Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes. J. Biol. Chem. 279:23615-21
Abstract	The collagen prolyl hydroxylases are enzymes that are required for proper collagen biosynthesis, folding, and assembly. They reside within the endoplasmic reticulum and belong to the group of 2-oxoglutarate and iron-dependent dioxygenases. Although prolyl 4-hydroxylase has been characterized as an alpha2beta2 tetramer in which protein disulfide isomerase is the beta subunit with two different alpha subunit isoforms, little is known about the enzyme prolyl 3-hydroxylase (P3H). It was initially characterized and shown to have an enzymatic activity distinct from that of prolyl 4-hydroxylase, but no amino acid sequences or genes were ever reported for the mammalian enzyme. Here we report the characterization of a novel prolyl 3-hydroxylase enzyme isolated from embryonic chicks. The primary structure of the enzyme, which we now call P3H1, demonstrates that P3H1 is a member of a family of prolyl 3-hydroxylases, which share the conserved residues present in the active site of prolyl 4-hydroxylase and lysyl hydroxylase. P3H1 is the chick homologue of mammalian leprecan or growth suppressor 1. Two other P3H family members are the genes previously called MLAT4 and GRCB. In this study we demonstrate prolyl 3-hydroxylase activity of the purified enzyme P3H1 on a full-length procollagen substrate. We also show it to specifically interact with denatured collagen and to exist in a tight complex with other endoplasmic reticulum-resident proteins. Immunohistochemistry with a monoclonal antibody specific for chick P3H1 localizes P3H1 specifically to tissues that express fibrillar collagens, suggesting that other P3H family members may be responsible for modifying basement membrane collagens.
Links	PubMed Online version:10.1074/jbc.M312807200
Keywords	Amino Acid Sequence; Animals; Chick Embryo; Collagen/metabolism; Embryo, Nonmammalian/enzymology; Molecular Sequence Data; Organ Specificity; Procollagen-Proline Dioxygenase/analysis; Procollagen-Proline Dioxygenase/chemistry; Procollagen-Proline Dioxygenase/classification; Procollagen-Proline Dioxygenase/genetics; Sequence Alignment; Substrate Specificity
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:P3H1	enables	GO:0019797: procollagen-proline 3-dioxygenase activity	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	F		Seeded From UniProt	complete
HUMAN:P3H1	part_of	GO:0032991: protein-containing complex	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	C		Seeded From UniProt	complete
HUMAN:P3H1	enables	GO:0005515: protein binding	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	F	has_input:(UniProtKB:O75718) has_input:(UniProtKB:P23284)	Seeded From UniProt	complete
HUMAN:P3H1	contributes_to	GO:0005518: collagen binding	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	F	has_input:(UniProtKB:O75718) has_input:(UniProtKB:P23284)	Seeded From UniProt	complete
HUMAN:P3H1	involved_in	GO:0032963: collagen metabolic process	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	P		Seeded From UniProt	complete
HUMAN:P3H1	involved_in	GO:0061077: chaperone-mediated protein folding	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q6JHU8	P	has_input:(UniProtKB:O75718) has_input:(UniProtKB:P23284)|results_in_maturation_of(GO:0005586)	Seeded From UniProt	complete
MOUSE:P3H1	enables	GO:0019797: procollagen-proline 3-dioxygenase activity	ECO:0000266: sequence orthology evidence used in manual assertion	UniProtKB:Q6JHU8	F		Seeded From UniProt	complete
MOUSE:P3H1	located_in	GO:0005783: endoplasmic reticulum	ECO:0000266: sequence orthology evidence used in manual assertion	UniProtKB:Q6JHU8	C		Seeded From UniProt	complete
MOUSE:P3H1	involved_in	GO:0032963: collagen metabolic process	ECO:0000266: sequence orthology evidence used in manual assertion	UniProtKB:Q6JHU8	P		Seeded From UniProt	complete
CHICK:P3H1	located_in	GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
CHICK:P3H1	acts_upstream_of_or_within	GO:0032963: collagen metabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:P3H1	part_of	GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
CHICK:P3H1	enables	GO:0019797: procollagen-proline 3-dioxygenase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
CHICK:P3H1	involved_in	GO:0032963: collagen metabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.