1.4.3.13 Lysyl oxidases

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1.4.3.13 Lysyl oxidases

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Lysyl oxidases are extracellular enzymes that are vital for cross-linking fibrillar elastin and collagens and for extracellular matrix stabilisation [2,5,5]. LOX and LOXL2 are implicated in fibrosis, tumourigenesis, and metastasis [1], and are subsequently molecular targets for cancer drug discovery [6].

Enzymes

lysyl oxidase Show summary »« Hide summary More detailed page go icon to follow link

Target Id

3097

Nomenclature

lysyl oxidase

Previous and unofficial names

protein-lysine 6-oxidase

Genes

LOX (Hs), Lox (Mm), Lox (Rn)

Ensembl ID

ENSG00000113083 (Hs), ENSMUSG00000024529 (Mm), ENSRNOG00000014426 (Rn)

UniProtKB AC

P28300 (Hs), P28301 (Mm)

EC number

1.4.3.13

H₂O + L-lysyl-[protein] + O₂ = [protein]-(S)-2-amino-6-oxohexanoate + H₂O₂ + NH₄⁺

Comment

The amine oxidase activity of the mature LOX enzyme is required for the crosslinking of collagens and elastin. The propeptide has regulatory functions as a tumour suppressor.

lysyl oxidase like 2 Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2853

Nomenclature

lysyl oxidase like 2

Previous and unofficial names

LOR2 | WS9-14 | protein-lysine 6-oxidase | lysyl oxidase homolog 2 | lysyl oxidase-like 2

Genes

LOXL2 (Hs), Loxl2 (Mm), Loxl2 (Rn)

Ensembl ID

ENSG00000134013 (Hs), ENSMUSG00000034205 (Mm), ENSRNOG00000016758 (Rn)

UniProtKB AC

Q9Y4K0 (Hs), P58022 (Mm), B5DF27 (Rn)

EC number

1.4.3.13	H₂O + L-lysyl-[protein] + O₂ = [protein]-(S)-2-amino-6-oxohexanoate + H₂O₂ + NH₄⁺
Reaction is required for collagen and elastin cross-linking in the biosynthesis of normal mature extracellular matrices. peptidyl-L-lysyl-peptide + O₂ + H₂O = peptidyl-allysyl-peptide + NH₃ + H₂O₂ [3]

Comment

Circulating LOXL2 has been identified as a surrogate biomarker of metastasis for breast cancers [4].

References

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1. Barker HE, Chang J, Cox TR, Lang G, Bird D, Nicolau M, Evans HR, Gartland A, Erler JT. (2011) LOXL2-mediated matrix remodeling in metastasis and mammary gland involution. Cancer Res, 71 (5): 1561-72. [PMID:21233336]

2. Csiszar K. (2001) Lysyl oxidases: a novel multifunctional amine oxidase family. Prog Nucleic Acid Res Mol Biol, 70: 1-32. [PMID:11642359]

3. Harris ED, Gonnerman WA, Savage JE, O'Dell BL. (1974) Connective tissue amine oxidase. II. Purification and partial characterization of lysyl oxidase from chick aorta. Biochim Biophys Acta, 341 (2): 332-44. [PMID:4838158]

4. Janyasupab M, Lee YH, Zhang Y, Liu CW, Cai J, Popa A, Samia AC, Wang KW, Xu J, Hu CC et al.. (2015) Detection of Lysyl Oxidase-Like 2 (LOXL2), a Biomarker of Metastasis from Breast Cancers Using Human Blood Samples. Recent Pat Biomark, 5 (2): 93-100. [PMID:28670509]

5. Molnar J, Fong KS, He QP, Hayashi K, Kim Y, Fong SF, Fogelgren B, Szauter KM, Mink M, Csiszar K. (2003) Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Biochim Biophys Acta, 1647 (1-2): 220-4. [PMID:12686136]

6. Smithen DA, Leung LMH, Challinor M, Lawrence R, Tang H, Niculescu-Duvaz D, Pearce SP, Mcleary R, Lopes F, Aljarah M et al.. (2020) 2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth. J Med Chem, 63 (5): 2308-2324. [PMID:31430136]

How to cite this family page

Database page citation:

1.4.3.13 Lysyl oxidases. Accessed on 26/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=912.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.