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Information on EC 1.4.3.13 - protein-lysine 6-oxidase and Organism(s) Rattus norvegicus and UniProt Accession P16636
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1.4.3.13 protein-lysine 6-oxidaseIUBMB Comments
Also acts on protein 5-hydroxylysine. This enzyme catalyses the final known enzymic step required for collagen and elastin cross-linking in the biosynthesis of normal mature extracellular matrices . These reactions play an important role for the development, elasticity and extensibility of connective tissue. The enzyme is also active on free amines, such as cadaverine or benzylamine [4,5]. Some isoforms can also use [protein]-N(6)-acetyl-L-lysine as substrate deacetamidating the substrate .
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Word Map
- 1.4.3.13
- collagen
- fibrosis
- metastasis
- fiber
- copper
-
crosslinking
- amine
-
elastic
- glaucoma
- aortic
-
stiff
- beta-aminopropionitrile
- tropoelastin
-
copper-dependent
-
fibril
- metalloproteinases
- procollagens
-
biomechanical
- propeptide
-
exfoliation
-
fibrillar
-
tensile
- myofibroblasts
- aneurysm
-
pseudoexfoliation
- cutis
-
copper-binding
- fibrillin-1
-
open-angle
- menkes
-
copper-deficient
-
prolapse
-
fibrillogenesis
-
cross-linkage
- desmosine
-
copper-containing
- medicine
- benzylamine
- diagnostics
-
pentosidine
- synthesis
-
microfibrillar
-
microfibrils
-
elastosis
- ehlers-danlos
-
elastolytic
-
col3a1
-
semicarbazide-sensitive
-
cuproenzymes
-
c-proteinase
-
fibulins
- hydroxylysine
-
pyridinoline
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Synonyms
lysyl oxidase, loxl2, loxl1, loxl4, loxl3, lox-pp, lysyl oxidases, lysyl oxidase-like 1, lysyl oxidase-like 2, lysyl oxidase-like, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
LOX
lysyl oxidase propetide
-
has biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation
RAS excision protein
-
-
-
-
LOX
-
LOXactivity is essential to generate optimal chemotactic sensitivity of cells to chemoattractants by oxidizing specific cell surface proteins, such as platelet-derived growth factor-beta
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[protein]-L-lysine + O2 + H2O = [protein]-(S)-2-amino-6-oxohexanoate + NH3 + H2O2
ping-pong mechanism of 2 half-reactions completing the catalytic cycle, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
oxidative deamination
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-L-lysine:oxygen 6-oxidoreductase (deaminating)
Also acts on protein 5-hydroxylysine. This enzyme catalyses the final known enzymic step required for collagen and elastin cross-linking in the biosynthesis of normal mature extracellular matrices [4]. These reactions play an important role for the development, elasticity and extensibility of connective tissue. The enzyme is also active on free amines, such as cadaverine or benzylamine [4,5]. Some isoforms can also use [protein]-N(6)-acetyl-L-lysine as substrate deacetamidating the substrate [6].
CAS REGISTRY NUMBER
COMMENTARY
99676-44-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
-
-
-
-
?
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
-
enzyme plays a critical role in the formation and repair of extracellular matrix, formation of cross-links in fibrillar collagen and elastin, only in fibrillar aggregates
-
-
?
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
-
in a variatey of basic globular proteins
i.e. peptidyl-L-alpha-aminoadipic-delta-semialdehyde
-
?
additional information
?
-
apparent lysyl oxidase isozymes contain a highly conserved LOX active site sequence in the nuclei of PC-12 cells
-
-
?
additional information
?
-
-
enzyme modifies cellular activity and can function as a messenger shuttling information between the intra- and extracellular compartments
-
-
?
additional information
?
-
-
enzyme contains a cytokine receptor domain, substrate specificity, preference for the L-lysine residues in the sequence N-acetyl-(Gly)4-Glu-Lys-(Gly)5-amide, enzyme is tightly associated to the substrates in connective tissue
-
-
?
additional information
?
-
-
lysyl oxidase is a copper-dependent amine oxidase that catalyzes the crosslinking of collagens and elastin, and is thus critical for the stability of the extracellular matrix
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
-
enzyme plays a critical role in the formation and repair of extracellular matrix, formation of cross-links in fibrillar collagen and elastin, only in fibrillar aggregates
-
-
?
additional information
?
-
-
enzyme modifies cellular activity and can function as a messenger shuttling information between the intra- and extracellular compartments
-
-
?
additional information
?
-
-
lysyl oxidase is a copper-dependent amine oxidase that catalyzes the crosslinking of collagens and elastin, and is thus critical for the stability of the extracellular matrix
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lysyl-tyrosyl quinone
-
essential LTQ cofactor, a unique carbonyl cofactor forming an intramolecular covalent bond, Lys314 and Tyr349 are progenitors of the cofactor, autcatalytic hydroxylation and oxidation of Tyr349, structure overview
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cu2+
Cu2+
-
enzyme has a copper-binding domain, copper-cofactor is required, tightly bound at the active site, may play a conformational role in the initial half-reaction
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
beta-aminopropionitrile
a highly specific lysyl oxidase inhibitor that reportedly blocks LOX inhibition of Ras-induced oocyte maturation
TNFalpha
-
TNFalpha decreases LOX mRNA levels in endothelial cells in a dose- and time-dependent manner (2fold at 1 ng/ml and maximum at 2.5 ng/ml) and endothelial LOX enzymatic activity
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tumor necrosis factor-alpha
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inhibits LOX mRNA transcription and LOX activity
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beta-aminopropionitrile
-
reduces LOX activity and significantly increases MCP-1 secretion in vascular smooth uscle cells
additional information
-
hypercholesterolemia down-regulates LOX expression and activity
-
additional information
-
TNF-alpha-stimulated matrix metalloproteinase-9 expression and Erk1/2 activation are both significantly inhibited by LOX-PP
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
transforming growth factor-beta1
-
fibrogenic cytokine, strongly promotes enzyme expression in fibroblasts of neonatal rat lung, human embryos and rat vascular smooth muscle cells
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
apparent lysyl oxidase isozymes contain a highly conserved LOX active site sequence in the nuclei of PC-12 cells
additional information
-
different spatial and temporal expression of LOX and LOXL1 during growth and aging, expression analysis of LOXL1 and LOX in the aorta during the development, growth, and aging of LOU rats, overview
additional information
quantitative expression analysis of LOX isozymes in different subcellular compartments in PC-12 cells, overview
additional information
-
high aortic LOX expression early in the development, i.e. embryonic day 15, followed by a drastic reduction in adulthood, whereas LOXL1 is mainly detectable in the intima and media and is expressed throughout life in the LOU rat
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
quantitative expression analysis of LOX isozymes, overview
-
inactive proenzyme proLO is secreted into the medium of cell culture
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
LOX is the principal enzyme involved in crosslinking of collagen. Nuclear lysyl oxidase probably regulates nuclear growth, and thereby modulates cell proliferation, overview
metabolism
-
the enzyme is linked to crosslinking of elastin and collagen, it enhances tropoelastin crosslinking into matrix structures and elastin synthesis and matrix yield, overview
physiological function
physiological function
-
lysyl oxidase is a copper-dependent amine oxidase that catalyzes the crosslinking of collagens and elastin, and is thus critical for the stability of the extracellular matrix. LOX mediates suppression of MCP-1, one of the highly upregulated chemokines, and subsequent inflammatory responses, overview
physiological function
-
role for lysyl oxidase-like, LOXL1, in adult elastin synthesis and a role for its isoform, lysyl oxidase, LOX, in the synthesis of both collagens and elastin during development. Specific roles for LOX and LOXL1 in the synthesis and remodeling of elastic and collagen fibers, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LYOX_RAT
411
0
46559
Swiss-Prot
Secretory Pathway (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32000
50000
-
x * 50000, proenzyme form, DNA sequence calculation, x * 32000, active enzyme, SDS-PAGE
32000
-
x * 50000, proenzyme form, DNA sequence calculation, x * 32000, active enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
structural implications of primary sequence, profile of ionic residues, overview
?
-
x * 50000, proenzyme form, DNA sequence calculation, x * 32000, active enzyme, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
proenzyme proLO contains a catalysis-suppressing domain, cleavage site is Gly162-Asp163, and an N-terminal signal peptide, cleavage site is Cys21-Ala22, cleavage of the proenzyme domain by metalloendoprotease procollagen C-proteinase
additional information
-
LOX suffers different posttranslational modifications including signal peptide cleavage, glycosylation, copper incorporation and formation of the lysyl-tyrosyl-quinone cofactor
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genes and isozymes LOXL1 and LOX, detailed expression analysis in aorta during growth and development, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
synthesis
-
required for the normal biosynthesis and maturation of collagen and elastin
medicine
-
increase in the expression of lysyl oxidase during wound healing in skin and in aorta, lung and skin of developing and aging rats. Implication of lysyl oxidase as a target gene for IRF-1 in tumor suppression. Lysly oxidase has unusual and important roles in cellular homeostasis
medicine
-
chronic inhalation of cadmium induces emphysema. Long-term Cd exposure induces inhibition of Cu-dependent lysyl oxidase and its substrates, by upregulation of Cu scavenging thiols in pulmonary fibroblasts. Downregulation of lysyl oxidase results from limitated Cu bioavailability as a central event contributing to Cd-induced extracellular matrix damage. Restoration of LO levels in Cd-insulted lung cells or tissues by replenishing Cu may have a protective or therapeutic effect on Cd-induced emphysema
medicine
-
treatment of rat dermal wound with lysyl oxidase-producing gene activated matrix leads to significantly enhanced mechanical strength of the wound site
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Smith-Mungo, L.I.; Kagan, H.M.
Lysyl oxidase: properties, regulation and multiple functions in biology
Matrix Biol.
16
387-398
1998
Bos taurus, Saccharomyces cerevisiae, Gallus gallus, Ovis aries, Homo sapiens, Mammalia, Mus musculus, Rattus norvegicus
Kagan, H.M.; Li, W.
Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell
J. Cell. Biochem.
88
660-672
2003
Bos taurus, Homo sapiens, Rattus norvegicus
Lau, Y.K.; Gobin, A.M.; West, J.L.
Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing
Ann. Biomed. Eng.
34
1239-1246
2006
Rattus norvegicus
Zhao, Y.; Gao, S.; Chou, I.N.; Toselli, P.; Stone, P.; Li, W.
Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts
Toxicol. Sci.
90
478-489
2006
Rattus norvegicus
Rodriguez, C.; Alcudia, J.F.; Martinez-Gonzalez, J.; Raposo, B.; Navarro, M.A.; Badimon, L.
Lysyl oxidase (LOX) down-regulation by TNFalpha: a new mechanism underlying TNFalpha-induced endothelial dysfunction
Atherosclerosis
196
558-564
2008
Bos taurus, Homo sapiens, Rattus norvegicus, Sus scrofa
Hurtado, P.A.; Vora, S.; Sume, S.S.; Yang, D.; St Hilaire, C.; Guo, Y.; Palamakumbura, A.H.; Schreiber, B.M.; Ravid, K.; Trackman, P.C.
Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation
Biochem. Biophys. Res. Commun.
366
156-161
2008
Rattus norvegicus
Buchinger, B.; Spitzer, S.; Karlic, H.; Klaushofer, K.; Varga, F.
Lysyl oxidase (LOX) mRNA expression and genes of the differentiated osteoblastic phenotype are upregulated in human osteosarcoma cells by suramin
Cancer Lett.
265
45-54
2008
Homo sapiens, Rattus norvegicus
Alcudia, J.F.; Martinez-Gonzalez, J.; Guadall, A.; Gonzalez-Diez, M.; Badimon, L.; Rodriguez, C.
Lysyl oxidase and endothelial dysfunction: mechanisms of lysyl oxidase down-regulation by pro-inflammatory cytokines
Front. Biosci.
13
2721-2727
2008
Rattus norvegicus, Sus scrofa
Gao, S.; Zhao, Y.; Kong, L.; Toselli, P.; Chou, I.N.; Stone, P.; Li, W.
Cloning and characterization of the rat lysyl oxidase gene promoter: identification of core promoter elements and functional nuclear factor I-binding sites
J. Biol. Chem.
282
25322-25337
2007
Rattus norvegicus
Lucero, H.A.; Ravid, K.; Grimsby, J.L.; Rich, C.B.; Dicamillo, S.J.; Maeki, J.M.; Myllyharju, J.; Kagan, H.M.
Lysyl oxidase oxidizes cell membrane proteins and enhances the chemotactic response of vascular smooth muscle cells
J. Biol. Chem.
283
24103-24117
2008
Mus musculus, Rattus norvegicus
Onoda, M.; Yoshimura, K.; Aoki, H.; Ikeda, Y.; Morikage, N.; Furutani, A.; Matsuzaki, M.; Hamano, K.
Lysyl oxidase resolves inflammation by reducing monocyte chemoattractant protein-1 in abdominal aortic aneurysm
Atherosclerosis
208
366-369
2009
Rattus norvegicus
Kothapalli, C.R.; Ramamurthi, A.
Lysyl oxidase enhances elastin synthesis and matrix formation by vascular smooth muscle cells
J. Tissue Eng. Regen. Med.
3
655-661
2009
Bos taurus, Rattus norvegicus
Behmoaras, J.; Slove, S.; Seve, S.; Vranckx, R.; Sommer, P.; Jacob, M.P.
Differential expression of lysyl oxidases LOXL1 and LOX during growth and aging suggests specific roles in elastin and collagen fiber remodeling in rat aorta
Rejuvenation Res.
11
883-889
2008
Rattus norvegicus
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