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Literature summary extracted from

  • Chen, Y.; Terajima, M.; Yang, Y.; Sun, L.; Ahn, Y.H.; Pankova, D.; Puperi, D.S.; Watanabe, T.; Kim, M.P.; Blackmon, S.H.; Rodriguez, J.; Liu, H.; Behrens, C.; Wistuba, I.I.; Minelli, R.; Scott, K.L.; Sanchez-Adams, J.; Guilak, F.; Pati, D.; Thilaganathan, N.; Burns, A.R.; Creighton, C.J.; Martinez, E.D.; Zal, T.; Allen, K.; Yamauchi, M.; Kurie, J.M.
    Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma (2015), J. Clin. Invest., 125, 1147-1162 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.14.11.4 medicine isozyme LH2 is of interest as candidate mediator of a p21-independent transcriptional program that regulates the metastatic propensity of KC cells. LH2 promotes lung cancer metastatic behavior and predicts poor prognosis in patients Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.11.4 gene PLOD2 Homo sapiens
1.14.11.4 gene PLOD2 Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
1.14.11.4 additional information in syngeneic wild-type Cdkn1a mice, LH2-deficient KC2 tumors are smaller and generate fewer lung metastases than KC2 tumors transfected with scrambled shRNA do Mus musculus
1.14.11.4 additional information overexpression of isozyme LH2 in osteoblasts induces a switch in the predominant type of collagen cross-link from LCC to HLCC, which qualitatively affects fibrillogenesis and matrix organization Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.11.4 [procollagen]-L-lysine + 2-oxoglutarate + O2 Homo sapiens
-
 [procollagen]-(2S,5R)-5-hydroxy-L-lysine + succinate + CO2
-
 ?
1.14.11.4 [procollagen]-L-lysine + 2-oxoglutarate + O2 Mus musculus
-
 [procollagen]-(2S,5R)-5-hydroxy-L-lysine + succinate + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.11.4 Homo sapiens O00469
-
-
1.14.11.4 Mus musculus Q9R0B9 Cdkn1a-null mice
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.11.4 adenocarcinoma cell p21-deficient (KC) and -replete (K) murine lung adenocarcinoma cells, increased LH2 enzyme activity Mus musculus
-
1.14.11.4 fibroblast skin Homo sapiens
-
1.14.11.4 fibroblast skin Mus musculus
-
1.14.11.4 lung
-
 Homo sapiens
-
1.14.11.4 lung
-
 Mus musculus
-
1.14.11.4 lung adenocarcinoma cell line 4 lung adenocarcinoma cell lines (KC1Ā–KC4) from lung tumors in KC mice and 2 lung adenocarcinoma cell lines (K1 and K2) from Cdkn1aWT K-rasLA1 mice. Expression levels of the third gene of interest, LH2, are 10-30 times higher in the highly metastatic KC cells and include both LH2 isoforms, full-length (LH2b) and spliced at exon 13 (LH2a) Mus musculus
-
1.14.11.4 lung cancer cell increased LH2 enzyme activity in lung carcinoma compared to healthy lung Homo sapiens
-
1.14.11.4 skin
-
 Homo sapiens
-
1.14.11.4 skin
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.11.4 [procollagen]-L-lysine + 2-oxoglutarate + O2
-
 Homo sapiens [procollagen]-(2S,5R)-5-hydroxy-L-lysine + succinate + CO2
-
 ?
1.14.11.4 [procollagen]-L-lysine + 2-oxoglutarate + O2
-
 Mus musculus [procollagen]-(2S,5R)-5-hydroxy-L-lysine + succinate + CO2
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.11.4 LH2
-
 Homo sapiens
1.14.11.4 LH2
-
 Mus musculus
1.14.11.4 lysyl hydroxylase 2
-
 Homo sapiens
1.14.11.4 lysyl hydroxylase 2
-
 Mus musculus
1.14.11.4 PLOD2
-
 Homo sapiens
1.14.11.4 PLOD2
-
 Mus musculus
1.14.11.4 procollagen-lysine, 2-oxoglutarate 5-dioxygenase
-
 Homo sapiens
1.14.11.4 procollagen-lysine, 2-oxoglutarate 5-dioxygenase
-
 Mus musculus

General Information

EC Number General Information Comment Organism
1.14.11.4 malfunction patients with Bruck syndrome, a recessively inherited disorder with inactivating mutations in the gene encoding LH2 (PLOD2/LH2), have traits of osteogenesis imperfecta with congenital contractures of the large joints. Conversely, skin fibroblasts from patients with systemic sclerosis, a fibrotic disease involving skin and other organs, have elevated LH2 expression and increased production of HLCCs Homo sapiens
1.14.11.4 physiological function intracellular procollagen-lysine, 2-oxoglutarate 5-dioxygenase enzymes induce hydroxylation of Lys residues on collagen prior to formation of triple helical pro-collagen molecules. Following secretion of pro-collagen molecules into the extracellular space, the telopeptidyl Hyl residues undergo LOX-induced oxidative deamination into Hylald, which then forms Hylald-derived aldimine cross-links that spontaneously rearrange into stable ketoamines; these further mature into stable Hylald-derived collagen cross-links (HLCCs). Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. Epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen crosslinks. Ectopic LH2 expression increases cell migration and invasion in Boyden chambers and enhances tumor growth and metastatic capacity in syngeneic wild-type Cdkn1a mice Mus musculus
1.14.11.4 physiological function intracellular procollagen-lysine, 2-oxoglutarate 5-dioxygenase enzymes induce hydroxylation of Lys residues on collagen prior to formation of triple helical pro-collagen molecules. Following secretion of pro-collagen molecules into the extracellular space, the telopeptidyl Hyl residues undergo LOX-induced oxidative deamination into Hylald, which then forms Hylald-derived aldimine cross-links that spontaneously rearrange into stable ketoamines; these further mature into stable Hylald-derived collagen cross-links (HLCCs). Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. Epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen crosslinks. relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde-derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Lysyl hydroxylase 2 (LH2) hydroxylates telopeptidyl lysine residues on collagen, and shifts the tumor stroma toward a high-HLCC, low-LCC state, increasing tumor stiffness, and enhancing tumor cell invasion and metastasis. LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma Homo sapiens