Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3 (PLOD3)
The protein contains 738 amino acids for an estimated molecular weight of 84785 Da.
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). (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs35627324 | |
| LH3 deficiency | |
| dbSNP:rs1134907 |
Biological Process
Basement membrane assembly
Cellular response to hormone stimulus
Collagen fibril organization
Collagen metabolic process
Endothelial cell morphogenesis
Epidermis morphogenesis
Hydroxylysine biosynthetic process
In utero embryonic development
Lung morphogenesis
Neural tube development
Peptidyl-lysine hydroxylation
Protein localization
Protein O-linked glycosylation
Vasodilation
The reference OMIM entry for this protein is 603066
Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3; plod3
Lysine hydroxylase 3; lh3
Lysyl hydroxylase 3
DESCRIPTION
Lysyl hydroxylase (LH; EC 1.14.11.4), a member of the 2-oxoglutarate-dependent dioxygenase family, is an enzyme modifying lysyl residues in collagens. LH has 3 different isoenzymes encoded by 3 different genes: LH1, encoded by PLOD1 (153454); LH2, encoded by PLOD2 (601865); and LH3, encoded by PLOD3. In addition to LH activity, LH3 has also collagen galactosyltransferase (GT; EC 2.4.1.50) and glucosyltransferase (GGT; EC 2.4.1.66) activity (Salo et al., 2008).CLONING
Passoja et al. (1998) cloned human lysyl hydroxylase-3. The LH3 cDNA clones encode a 738-amino acid polypeptide, including a signal peptide of 24 residues. The overall amino acid sequence identity between the processed human PLOD3 and PLOD1 polypeptides is 59%, and that between the processed PLOD3 and PLOD2 polypeptides is 57%, whereas the identity to the processed Caenorhabditis elegans polypeptide is only 45%. All 4 critical residues at the catalytic site, 2 histidines, 1 aspartate, and 1 arginine, are conserved in all of these polypeptides. The mRNA for PLOD3 was found to be expressed in a variety of tissues, but distinct differences appeared to exist in the expression pattern of the 3 isoenzyme mRNAs. Recombinant PLOD3 expressed in insect cells by means of a baculovirus vector was found to be more soluble than PLOD1 expressed in the same cell type. No differences in catalytic properties were found between the recombinant PLOD3 and PLOD1 isoenzymes. Deficiency in lysyl hydroxylase-1 activity is known to cause the type VI variant of the Ehlers-Danlos syndrome (225400); it was considered possible that deficiency in PLOD3 leads to some other variant of EDS or to some other heritable disorder of connective tissue. Independently and simultaneously, Valtavaara et al. (1998) characterized the lysyl hydroxylase-3 gene. They found that expression of PLOD3 is highly regulated in adult human tissues. A strong hybridization signal, corresponding to a 2.75-kb mRNA, was obtained in heart, placenta, and pancreas on multiple tissue RNA blots. Expression of the cDNA in vitro resulted in the synthesis of a protein that hydroxylates lysyl residues in collagenous sequences in a non-triple helical conformation.MAPPING
Valtavaara et al. (1998) mapped the PLOD3 gene to chromosome 7 by Southern blot analysis of 13 human/rodent hybrid clones and to 7q22 by fluorescence in situ hybridization. They mapped the homologous rat gene to chromosome 12. Human chromosome 7 and rat chromosome 12 are known to be partially homologous as indicated by conserved synteny. Sipila et al. (2000) mapped the mouse homolog to chromosome 5.GENE FUNCTION
Heikkinen et al. (2000) determined that PLOD3, transfected and expressed by sf9 insect cells and by COS-7 cells, showed both lysyl hydroxylase and collagen GGT activity. Expression of PLOD3 in both systems resulted in secretion of enzyme. By mutation analysis, Heikkinen et al. (2000) showed that loss of the last 70 C-terminal amino acids of PLOD3 resulted in an enzyme that retained about half of the GGT activity but had no LH activity. Further, an asp669-to-ala mutation decreased LH activity and had no effect on GGT activity. Neither PLOD1 nor PLOD2 displayed GGT activity.MOLECULAR GENETICS
Salo et al. (2008) studied a female patient with a unique connective tissue disorder consisting of craniofacial dysmorphism, sensorineural deafness, skeletal features consisting of progressive scoliosis, talipes e ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 603066 was added.
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).