Leprecan

P3H1
Identifiers
Aliases	P3H1, GROS1, OI8, LEPRE1, prolyl 3-hydroxylase 1
External IDs	OMIM: 610339; MGI: 1888921; HomoloGene: 10509; GeneCards: P3H1; OMA:P3H1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)1 Band 1p34.2 Start 42,746,335 bp1 End 42,767,084 bp1
Gene location (Mouse) Chr. Chromosome 4 (mouse)2 Band 4|4 D2.1 Start 119,090,112 bp2 End 119,106,172 bp2
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium anterior pituitary tibial nerve tibia cartilage tissue right ovary left ovary canal of the cervix ascending aorta body of uterus Top expressed in calvaria cumulus cell tail of embryo dermis genital tubercle molar fossa facial skeleton umbilical cord long bone More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding L-ascorbic acid binding collagen binding protein-containing complex binding dioxygenase activity metal ion binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen oxidoreductase activity procollagen-proline 3-dioxygenase activity molecular function protein binding Cellular component protein-containing complex endoplasmic reticulum lumen membrane extracellular region endoplasmic reticulum extracellular exosome collagen-containing extracellular matrix Biological process regulation of protein secretion protein stabilization protein folding negative regulation of post-translational protein modification bone development negative regulation of cell population proliferation protein hydroxylation chaperone-mediated protein folding peptidyl-proline hydroxylation collagen metabolic process positive regulation of neuron projection development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64175 56401 Ensembl ENSG00000117385 ENSMUSG00000028641 UniProt Q32P28 Q3V1T4 RefSeq (mRNA) NM_001146289 NM_001243246 NM_022356 NM_001042411 NM_001286148 NM_019782 NM_019783 RefSeq (protein) NP_001139761 NP_001230175 NP_071751 NP_001035874 NP_001273077 NP_062756 NP_062757 Location (UCSC) Chr 1: 42.75 – 42.77 Mb Chr 4: 119.09 – 119.11 Mb PubMed search 3 4
Wikidata
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Leprecan (P3H1) is a protein associated with osteogenesis imperfecta⁵ type VIII.

Leprecan is part of a superfamily of 2OG-Fe(II) dioxygenase, along with DNA repair protein AlkB, and disease resistant EGL-9. The enzyme was found to be a type of hydroxylases used in the substrate formation of protein glycosylation.⁶

Leprecan, a proteoglycan, has demonstrated prolyl hydroxylase activity; prolyl hydroxylases hydroxylate proline residues.⁷ Prolyl 3-hydroxylase 1, P3H1, forms a larger complex with CRTAP and cyclophilin B, CyPB, in the endoplasimic reticulum. The complex hydroxylates a single proline residue, Pro986, on collagen chains.⁸ Recessive forms of Osteogenesis Imperfecta are partly caused by a mutation in the LEPRE1 gene. The mutation in the gene encodes prolyl 3-hydroxylase 1. The malfunctioning prolyl 3-hydroxylase in leprecan leads to inappropriate collagen folding. This is due to the instability caused by the absence of hydroxyproline. Hydroxyproline is the product of hydroxylating a proline residue.⁹

Leprecan, also known as P3H1, forms a tight complex with CRTAP and cyclophilin B (PPIB), a collagen processing enzyme complex named PCP complex (P3H1-CRTAP-PPIB). Cryo-electron microscopy (cryo-EM) studies have revealed that the PCP complex consists of P3H1, CRTAP, and PPIB in a 1:1:1 stoichiometry.¹⁰ The complex features a "face-to-face" spatial arrangement, with the prolyl hydroxylation site of the C-terminal domain of P3H1 and the prolyl isomerization site of PPIB positioned at the "top" of the complex. Below these dual-catalytic sites lies an X-shaped base formed by CRTAP and the N-terminal domain of P3H1, which exhibit similar 3D foldings. The surface of the PCP complex also harbors several potential collagen-binding sites, as indicated by EM density corresponding to a synthetic peptide with the COL1A1 sequence. Furthermore, the PCP complex has the ability to dimerize, forming a hexameric structure.