PLOD3

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 is an enzyme that in humans is encoded by the PLOD3 gene.^[5][6][7]

PLOD3
Identifiers
Aliases	PLOD3, LH3, procollagen-lysine,2-oxoglutarate 5-dioxygenase 3
External IDs	OMIM: 603066; MGI: 1347008; HomoloGene: 843; GeneCards: PLOD3; OMA:PLOD3 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q22.1 Start 101,205,977 bp[1] End 101,218,420 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 G2|5 76.09 cM Start 137,015,873 bp[2] End 137,025,502 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium pancreatic ductal cell tibial nerve mucosa of transverse colon C1 segment body of uterus granulocyte upper lobe of left lung muscle layer of sigmoid colon right lobe of liver Top expressed in granulocyte calvaria yolk sac stroma of bone marrow ankle joint tibiofemoral joint gastrula lactiferous gland muscle of thigh ventricular zone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function iron ion binding L-ascorbic acid binding dioxygenase activity metal ion binding protein binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen procollagen galactosyltransferase activity oxidoreductase activity procollagen-lysine 5-dioxygenase activity procollagen glucosyltransferase activity catalytic activity transferase activity glycosyltransferase activity Cellular component rough endoplasmic reticulum membrane endoplasmic reticulum membrane membrane extracellular exosome endoplasmic reticulum Golgi apparatus trans-Golgi network extracellular matrix extracellular region extracellular space endoplasmic reticulum lumen rough endoplasmic reticulum collagen-containing extracellular matrix Biological process protein localization lung morphogenesis collagen fibril organization epidermis morphogenesis endothelial cell morphogenesis vasodilation in utero embryonic development basement membrane assembly cellular response to hormone stimulus neural tube development protein O-linked glycosylation hydroxylysine biosynthetic process peptidyl-lysine hydroxylation collagen metabolic process metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8985 26433 Ensembl ENSG00000106397 ENSMUSG00000004846 UniProt O60568 Q9R0E1 RefSeq (mRNA) NM_001084 NM_011962 RefSeq (protein) NP_001075 NP_036092 Location (UCSC) Chr 7: 101.21 – 101.22 Mb Chr 5: 137.02 – 137.03 Mb PubMed search [3] [4]
Wikidata
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The protein encoded by this gene 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. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity.^[7]

Structure and functions

Cryo-electron microscopy (Cryo-EM) study has revealed the structural architecture of PLOD3 within the lysyl O-linked glycosylation complex (KOGG complex), which plays a crucial role in procollagen maturation. ^[8]

The KOGG complex consists of a PLOD3 (LH3) dimer, a Procollagen galactosyltransferase 1 (ColGalT1) dimer, and UDP-bound cofactors, orchestrating the hydroxylation (by PLOD3) and dual glycosylation (galactosylation by ColGalT1 and glucosylation by PLOD3) of lysine residues in the endoplasmic reticulum (ER) lumen. These modifications are essential for collagen cross-linking, fibrillogenesis, and overall structural integrity.

Additionally, the structural study suggests that the KOGG complex can polymerize into a larger, fiber-like enzyme supercomplex, which may further regulate collagen modification and assembly. Defects in PLOD3 function or glycosylation efficiency have been implicated in connective tissue disorders, including osteogenesis imperfecta and fibrosis-related diseases.