PLOD3

PLOD3 is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks.

Full Name

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3

Function

Multifunctional enzyme that catalyzes a series of essential post-translational modifications on Lys residues in procollagen (PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:30089812, PubMed:18834968).
Plays a redundant role in catalyzing the formation of hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:9582318, PubMed:9724729, PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:30089812, PubMed:18834968).
Plays a redundant role in catalyzing the transfer of galactose onto hydroxylysine groups, giving rise to galactosyl 5-hydroxylysine (PubMed:12475640, PubMed:18298658, PubMed:30089812, PubMed:18834968).
Has an essential role by catalyzing the subsequent transfer of glucose moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:10934207, PubMed:11896059, PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:30089812, PubMed:18834968).
Catalyzes hydroxylation and glycosylation of Lys residues in the MBL1 collagen-like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:25419660).
Essential for normal biosynthesis and secretion of type IV collagens (PubMed:18834968) (Probable). Essential for normal formation of basement membranes (By similarity).

Biological Process

Basement membrane assemblyIEA:Ensembl
Collagen fibril organizationTAS:Reactome
Collagen metabolic processIEA:Ensembl
Endothelial cell morphogenesisIEA:Ensembl
Epidermis morphogenesisIEA:Ensembl
Hydroxylysine biosynthetic processIEA:Ensembl
In utero embryonic developmentIEA:Ensembl
Lung morphogenesisIEA:Ensembl
Neural tube developmentIEA:Ensembl
Peptidyl-lysine hydroxylationManual Assertion Based On ExperimentIDA:CAFA
Protein localizationIEA:Ensembl
Protein O-linked glycosylationManual Assertion Based On ExperimentIMP:CAFA
VasodilationIEA:Ensembl

Cellular Location

Rough endoplasmic reticulum
Endoplasmic reticulum lumen
Endoplasmic reticulum membrane
Secreted
Secreted, extracellular space
The majority of the secreted protein is associated with the extracellular matrix.

Involvement in disease

Lysyl hydroxylase 3 deficiency (LH3 deficiency):
Connective tissue disorder. The syndrome is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders, most of them involving COL2A1 (type II collagen). The findings suggest that the failure of lysyl hydroxylation and hydroxylysyl carbohydrate addition, which affects many collagens, is the molecular basis of this syndrome.