PLOD3

PLOD3
Identifiers
Aliases	PLOD3, LH3, procollagen-lysine,2-oxoglutarate 5-dioxygenase 3
External IDs	OMIM: 603066; MGI: 1347008; GeneCards: PLOD3
Enzyme activity
Gene location (Human)
Chr.	Chromosome 7 (human)
End	101,218,420 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	137,025,502 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	8985
	26433
	ENSG00000106397
	ENSMUSG00000004846
	O60568
	Q9R0E1
	NM_001084
	NM_011962
	NP_001075
	NP_036092
	Wikidata
View/Edit Human	View/Edit Mouse

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 2 3 GRCh38: Ensembl release 89: ENSG00000106397 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004846 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Passoja K, Rautavuoma K, Ala-Kokko L, Kosonen T, Kivirikko KI (September 1998). "Cloning and characterization of a third human lysyl hydroxylase isoform". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10482–10486. Bibcode:1998PNAS...9510482P. doi:10.1073/pnas.95.18.10482. PMC 27920. PMID 9724729.
↑ Valtavaara M, Szpirer C, Szpirer J, Myllyla R (June 1998). "Primary structure, tissue distribution, and chromosomal localization of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3)". The Journal of Biological Chemistry. 273 (21): 12881–12886. doi:10.1074/jbc.273.21.12881. PMID 9582318.
1 2 "Entrez Gene: PLOD3 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3".
↑ Peng J, Li W, Yao D, Xia Y, Wang Q, Cai Y, et al. (March 2025). "The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation". Nature Communications. 16 (1) 2436. doi:10.1038/s41467-025-57768-9. PMC 11897130. PMID 40069201.

Salo AM, Wang C, Sipilä L, Sormunen R, Vapola M, Kervinen P, et al. (June 2006). "Lysyl hydroxylase 3 (LH3) modifies proteins in the extracellular space, a novel mechanism for matrix remodeling". Journal of Cellular Physiology. 207 (3): 644–653. doi:10.1002/jcp.20596. PMID 16447251. S2CID 19594208.
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, et al. (2005). "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 Research. 12 (2): 117–126. doi:10.1093/dnares/12.2.117. PMID 16303743.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 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.
Wang C, Luosujärvi H, Heikkinen J, Risteli M, Uitto L, Myllylä R (November 2002). "The third activity for lysyl hydroxylase 3: galactosylation of hydroxylysyl residues in collagens in vitro". Matrix Biology. 21 (7): 559–566. doi:10.1016/S0945-053X(02)00071-9. PMID 12475640.
Rautavuoma K, Takaluoma K, Passoja K, Pirskanen A, Kvist AP, Kivirikko KI, et al. (June 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". The Journal of Biological Chemistry. 277 (25): 23084–23091. doi:10.1074/jbc.M112077200. PMID 11956192.
Ruotsalainen H, Vanhatupa S, Tampio M, Sipilä L, Valtavaara M, Myllylä R (April 2001). "Complete genomic structure of mouse lysyl hydroxylase 2 and lysyl hydroxylase 3/collagen glucosyltransferase". Matrix Biology. 20 (2): 137–146. doi:10.1016/S0945-053X(01)00130-5. PMID 11334715.
Heikkinen J, Risteli M, Wang C, Latvala J, Rossi M, Valtavaara M, et al. (November 2000). "Lysyl hydroxylase 3 is a multifunctional protein possessing collagen glucosyltransferase activity". The Journal of Biological Chemistry. 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 Biology. 19 (1): 73–79. doi:10.1016/S0945-053X(99)00058-X. PMID 10686427.

This article on a gene on human chromosome 7 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000106397 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[Passoja_1998-5] Passoja K, Rautavuoma K, Ala-Kokko L, Kosonen T, Kivirikko KI (September 1998). "Cloning and characterization of a third human lysyl hydroxylase isoform". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10482–10486. Bibcode:1998PNAS...9510482P. doi:10.1073/pnas.95.18.10482. PMC 27920. PMID 9724729.

[Valtavaara_1998-6] Valtavaara M, Szpirer C, Szpirer J, Myllyla R (June 1998). "Primary structure, tissue distribution, and chromosomal localization of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3)". The Journal of Biological Chemistry. 273 (21): 12881–12886. doi:10.1074/jbc.273.21.12881. PMID 9582318.

[entrez-7] 1 2 "Entrez Gene: PLOD3 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3".

[8] Peng J, Li W, Yao D, Xia Y, Wang Q, Cai Y, et al. (March 2025). "The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation". Nature Communications. 16 (1) 2436. doi:10.1038/s41467-025-57768-9. PMC 11897130. PMID 40069201.

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PLOD3

Structure and functions

References

Further reading