PLOD3

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

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.

References

1. GRCh38: Ensembl release 89: ENSG00000106397 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004846 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Passoja K, Rautavuoma K, Ala-Kokko L, Kosonen T, Kivirikko KI (Sep 1998). "Cloning and characterization of a third human lysyl hydroxylase isoform". Proc Natl Acad Sci U S A. 95 (18): 10482–10486. Bibcode:1998PNAS...9510482P. doi: 10.1073/pnas.95.18.10482 . PMC   27920 . PMID   9724729.
6. Valtavaara M, Szpirer C, Szpirer J, Myllyla R (Jun 1998). "Primary structure, tissue distribution, and chromosomal localization of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3)". J Biol Chem. 273 (21): 12881–12886. doi: 10.1074/jbc.273.21.12881 . PMID   9582318.
7. "Entrez Gene: PLOD3 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3".
8. Peng J, Li W, Yao D, Xia Y, Wang Q, Cai Y, Li S, Cao M, Shen Y, Ma P, Liao R, Zhao J, Qin A, Cao Y (2025-03-11). "The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation". Nature Communications. 16 (1). doi:10.1038/s41467-025-57768-9. ISSN   2041-1723.

Further reading

• Salo AM, Wang C, Sipilä L, et al. (2006). "Lysyl hydroxylase 3 (LH3) modifies proteins in the extracellular space, a novel mechanism for matrix remodeling". J. Cell. Physiol. 207 (3): 644–653. doi:10.1002/jcp.20596. PMID   16447251. S2CID   19594208.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–126. doi: 10.1093/dnares/12.2.117 . PMID   16303743.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature. 424 (6945): 157–164. Bibcode:2003Natur.424..157H. doi: 10.1038/nature01782 . PMID   12853948.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Wang C, Luosujärvi H, Heikkinen J, et al. (2003). "The third activity for lysyl hydroxylase 3: galactosylation of hydroxylysyl residues in collagens in vitro". Matrix Biol. 21 (7): 559–566. doi:10.1016/S0945-053X(02)00071-9. PMID   12475640.
• Rautavuoma K, Takaluoma K, Passoja K, et al. (2002). "Characterization of three fragments that constitute the monomers of the human lysyl hydroxylase isoenzymes 1–3. The 30-kDa N-terminal fragment is not required for lysyl hydroxylase activity". J. Biol. Chem. 277 (25): 23084–23091. doi: 10.1074/jbc.M112077200 . PMID   11956192.
• Ruotsalainen H, Vanhatupa S, Tampio M, et al. (2001). "Complete genomic structure of mouse lysyl hydroxylase 2 and lysyl hydroxylase 3/collagen glucosyltransferase". Matrix Biol. 20 (2): 137–146. doi:10.1016/S0945-053X(01)00130-5. PMID   11334715.
• Heikkinen J, Risteli M, Wang C, et al. (2000). "Lysyl hydroxylase 3 is a multifunctional protein possessing collagen glucosyltransferase activity". J. Biol. Chem. 275 (46): 36158–36163. doi: 10.1074/jbc.M006203200 . PMID   10934207.
• Rautavuoma K, Passoja K, Helaakoski T, Kivirikko KI (2000). "Complete exon-intron organization of the gene for human lysyl hydroxylase 3 (LH3)". Matrix Biol. 19 (1): 73–79. doi:10.1016/S0945-053X(99)00058-X. PMID   10686427.