Information on EC 1.4.3.13 - protein-lysine 6-oxidase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.4.3.13
-
RECOMMENDED NAME
GeneOntology No.
protein-lysine 6-oxidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
peptidyl-L-lysyl-peptide + O2 + H2O = peptidyl-allysyl-peptide + NH3 + H2O2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
oxidative deamination
-
-
-
-
redox reaction
-
-
-
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reduction
-
-
-
-
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].
CAS REGISTRY NUMBER
COMMENTARY hide
99676-44-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression is sensitively modulated by specific cytokines, growth factors and related intercellular molecular messengers
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,5-diaminopentane + O2 + H2O
? + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
6,6-dideutrolysine + O2 + H2O
? + NH3 + H2O2
show the reaction diagram
agmatine + O2 + H2O
?
show the reaction diagram
-
-
-
?
benzylamine + O2 + H2O
benzaldehyde + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
cadaverine + O2 + H2O
?
show the reaction diagram
collagen + H2O + O2
allysyl-collagen + NH3 + H2O2
show the reaction diagram
collagen + O2 + H2O
?
show the reaction diagram
-
collagen type I, II, III, IV, VI, VIII and X
-
-
?
collagen 2a1 + O2 + H2O
?
show the reaction diagram
A1L1V4, A6MH29, A6MH32, A6MH33, A6MH34, A6MH35, F1QQC3, Q6NYT8
-
-
-
?
collagen III + O2 + H2O
allysyl-collagen III + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
dichlorodihydrofluorescein diacetate + O2 + H2O
? + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
elastin + H2O + O2
allysyl-elastin + NH3 + H2O2
show the reaction diagram
elastin + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
histamine + O2 + H2O
?
show the reaction diagram
-
-
-
?
histone H1 + O2 + H2O
?
show the reaction diagram
histone H2 + O2 + H2O
?
show the reaction diagram
-
recombinant mature LOX and C-terminally deleted enzyme
-
-
?
lysine + O2 + H2O
?
show the reaction diagram
-
-
-
?
lysine:tyrosine (4:1) heteropolymer + O2 + H2O
? + NH3 + H2O2
show the reaction diagram
n-alkylamine + O2 + H2O
aldehyde + NH3 + H2O2
show the reaction diagram
peptidyl-L-hydroxylysyl-peptide + O2 + H2O
peptidyl-L-2-amino-5-hydroxy-6-oxohexanoyl-peptide + NH3 + H2O2
show the reaction diagram
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
show the reaction diagram
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-L-allysyl-peptide + NH3 + H2O2
show the reaction diagram
polylysine + O2 + H2O
allysine + H2O2 + NH3
show the reaction diagram
-
-
-
-
?
putrescine + O2 + H2O
?
show the reaction diagram
-
-
-
?
spermidine + O2 + H2O
?
show the reaction diagram
-
-
-
?
spermine + O2 + H2O
?
show the reaction diagram
-
-
-
?
tropoelastin + ?
?
show the reaction diagram
-
LOXL1 catalyzes the polymerization of tropoelastin
-
-
?
tropoelastin + H2O + O2
?
show the reaction diagram
-
-
-
?
tropoelastin + O2 + H2O
?
show the reaction diagram
-
-
-
?
tropoelastin + O2 + H2O
? + H2O2 + NH3
show the reaction diagram
-
oxidation of L-lysine residues, substrate from mammalia
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-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
collagen + H2O + O2
allysyl-collagen + NH3 + H2O2
show the reaction diagram
collagen III + O2 + H2O
allysyl-collagen III + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
elastin + H2O + O2
allysyl-elastin + NH3 + H2O2
show the reaction diagram
peptidyl-L-lysyl-peptide + O2 + H2O
peptidyl-allysyl-peptide + NH3 + H2O2
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
lysyl tyrosylquinone
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lysyl-tyrosyl quinone
lysyl-tyrosyl-quinone
lysyltyrosyl quinone
quinone
topaquinone
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i.e. TPQ or 2,4,5-trihydroxyphenylalanine quinone, formed by posttranslational modification of a tyrosine residue
trihydroxyphenylalanine quinone
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-
additional information
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enzyme contains a cross-linked quinone, cross-linking via lysyl- and tyrosyl residues
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
copper
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enzyme is a copper amino axidase, contains 1 type II copper atom per subunit
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1Z)-butanal thiosemicarbazone
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1-(3,5-diethoxypyridin-4-yl)methanamine dihydrochloride
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1-[3-(benzyloxy)-5-ethoxypyridin-4-yl]methanamine dihydrochloride
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2-Aminopropionitrile
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i.e. BAPN, is an irreversible inhibitor of LOX, involved in regulating the metastatic colonization potential of the human breast cancer cell line MDAMB-231
2-mercaptoethanol
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weakly inhibitory
2-mercaptopyridine-N-oxide
3,3'-[[4-(aminomethyl)pyridine-3,5-diyl]bis(oxy)]dipropan-1-ol dihydrochloride
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3,4-dihydroxybenzoate
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3-aminopropanenitrile
4,4'-[[4-(aminomethyl)pyridine-3,5-diyl]bis(oxy)]dibutan-1-ol dihydrochloride
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4-deoxypyridoxine
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pyridoxal analogue, 50% inhibition at 3 mM
alpha2-Macroglobulin
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-
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ascorbic acid
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inhibits the purified enzyme in vitro, and the formation of cross-linked collagen
basic fibroblast growth factor
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reduces enzyme expression in osteogenic cells
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beta-aminopropionitrile
cyclohexanone thiosemicarbazone
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cycloheximide
cyclopentanone thiosemicarbazone
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diethyldithiocarbamate
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Disulfiram
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a dithiocarbamate and Cu2+-chelator, inhibits the enzyme and causes teratogenic effects, malformations, distorted notochord development, and shortened anterior to posterior axis in zebrafish, overview
dithiothreitol
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-
erythorbic acid
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stereoisomer of ascorbic acid
glutathione
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slight inhibition
heparin
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homocysteine
homocysteine thiolactone
hydroxylamine
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Isonicotinic acid hydrazide
low-density lipoprotein
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N-[2-([2-[(1-oxidopyridin-2-yl)sulfanyl]ethyl]amino)ethyl]-5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamide
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fully effective at 0.02 mM
phenylhydrazine
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Semicarbazide
taurine
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tert-butyl [2-[(1-oxidopyridin-2-yl)sulfanyl]ethyl]carbamate
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fully effective at 0.002 mM
thiram
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a dithiocarbamate and Cu2+-chelator, inhibits the enzyme and causes teratogenic effects, malformations, distorted notochord development, and shortened anterior to posterior axis in zebrafish, overview
TNFalpha
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tumor necrosis factor-alpha
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VE-statin/egfl7 protein
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interacts with the catalytic domain of lysyl oxidase thereby preventing the crosslink of tropoelastin molecules into mature elastin polymers and regulating vascular elastogenesis
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vitamin B3
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Zn2+
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slightly inhibitory
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-aza-deoxycytidine
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activates LOXL2 gene expression
actinomycin D
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areca nut extract
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up-regulates LOX expression
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hypoxia inducible factor-1
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hypoxia-induced LOX expression is partially mediated by hypoxia inducible factor-1
nuclear factor I-A
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enhances lysyl oxidase promoter activities
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nuclear factor I-B
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enhances lysyl oxidase promoter activities
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pyridoxal
suramin
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0.15 mM, upregulates LOX expression
transforming growth factor beta
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increases LOX expression and activity
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transforming growth factor-beta1
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tumor growth factor-beta1
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stabilizes LOX mRNA leading to an increase in LOX activity
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additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
3,3'-[[4-(aminomethyl)pyridine-3,5-diyl]bis(oxy)]dipropan-1-ol dihydrochloride
Sus scrofa
P45845
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0.1
4,4'-[[4-(aminomethyl)pyridine-3,5-diyl]bis(oxy)]dibutan-1-ol dihydrochloride
Sus scrofa
P45845
-
additional information
additional information
Sus scrofa
P45845
above 1.0 mM for 1-(3,5-diethoxypyridin-4-yl)methanamine dihydrochloride and 1-[3-(benzyloxy)-5-ethoxypyridin-4-yl]methanamine dihydrochloride
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.054
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recombinant His-tagged LOXL1, substrate benzylamine
0.097
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recombinant His-tagged LOX, substrate benzylamine
0.15
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recombinant His-tagged LOXL2, substrate benzylamine
0.2
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about, retina
0.31
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purified recombinant enzyme, pH not specified in the publication, 37C
0.4
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about, lens
1.1
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about, iris/ciliary body
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7.7
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assay at
7.8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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LOX is highly expressed in early gestational amnion tissue (12-14 weeks)
Manually annotated by BRENDA team
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highly expressed in vascular lesions
Manually annotated by BRENDA team
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mineral-associated fraction
Manually annotated by BRENDA team
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LOX and LOXL
Manually annotated by BRENDA team
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LOX and LOXL
Manually annotated by BRENDA team
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LOX on the surface of pyramidal cells in the grey matter, LOXL in the nuclei of cortex cells and in the cytosol of capillary endothelial cells
Manually annotated by BRENDA team
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localization of LOX and LOXL in different tissue areas
Manually annotated by BRENDA team
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mature form of LOXL1 and polymerized LOXL1protein forms
Manually annotated by BRENDA team
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polymerized LOXL1protein forms
Manually annotated by BRENDA team
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of lung: LOX and LOXL, renal tubules: only LOXL, intestinal: only LOXL
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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of the stomach, mainly LOXL, mucous-secreting cells
Manually annotated by BRENDA team
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including dermal papillae, follicular sheaths, sebaceous glands
Manually annotated by BRENDA team
-
pyramidal cells: LOXL, not LOX
Manually annotated by BRENDA team
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epithelial cells, LOXL
Manually annotated by BRENDA team
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mature form of LOXL1 and polymerized LOXL1protein forms
Manually annotated by BRENDA team
-
LOX and LOXL, of skin epidermis and hair follicles
Manually annotated by BRENDA team
LOXL-1; LOXL-1, no expression of LOXL-2
Manually annotated by BRENDA team
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determination of LOX activity and expression in donor ocular tissues
Manually annotated by BRENDA team
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LOX gene expression is reduced in lung cancer cells
Manually annotated by BRENDA team
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in MCF-10A normal breast epithelial cells stably expressing lysyl oxidase LOX has no effect on cell proliferation. Coexpression of lysyl oxidase and placental lactogen leads to a 121% increase in cell proliferation
Manually annotated by BRENDA team
-
polymerized LOXL1protein forms
Manually annotated by BRENDA team
-
LOX mRNA is upregulated in OSCC cells
Manually annotated by BRENDA team
-
LOX gene expression is reduced in pancreatic cancer cells
Manually annotated by BRENDA team
apparent lysyl oxidase isozymes contain a highly conserved LOX active site sequence in the nuclei of PC-12 cells
Manually annotated by BRENDA team
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pepsin-secreting, in the basal part of the stomach, only LOX, no LOXL
Manually annotated by BRENDA team
-
LOXL2, LOX, LOXL
Manually annotated by BRENDA team
LOXL-1; LOXL-1, no expression of LOXL-2
Manually annotated by BRENDA team
-
determination of LOX activity and expression in donor ocular tissues
Manually annotated by BRENDA team
-
localization of LOX and LOXL in different tissue areas
Manually annotated by BRENDA team
-
LOXL2, LOX, LOXL
Manually annotated by BRENDA team
-
proliferating cell, LOXL expression, adult tissues
Manually annotated by BRENDA team
-
determination of LOX activity and expression in donor ocular tissues
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in differentiating cells
-
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
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x * 36000, recombinant processed LOX, SDS-PAGE, x * 51000, recombinant processed LOXL1, SDS-PAGE, x * 29000, recombinant processed LOXL2, SDS-PAGE
42000
-
mature enzyme, SDS-PAGE
49500
-
x * 49500, calculated from amino acid sequence
51000
-
x * 36000, recombinant processed LOX, SDS-PAGE, x * 51000, recombinant processed LOXL1, SDS-PAGE, x * 29000, recombinant processed LOXL2, SDS-PAGE
52000
-
x * 52000, extracellular LOXL, SDS-PAGE
59000
-
x * 59000, x * 61000, SDS-PAGE, may be isoenzymes or heterologous subunits
60000
-
x * 60000, SDS-PAGE
61000
-
x * 59000, x * 61000, SDS-PAGE, may be isoenzymes or heterologous subunits
80000
-
polymerized enzyme, SDS-PAGE
83600
x * 97000, including V5-epitope and histidine tag of 2.3 kDa, Western-Blot, x * 83600, calculated
85000
-
predicted molecular mass
93000
-
SDS-PAGE
97000
x * 97000, including V5-epitope and histidine tag of 2.3 kDa, Western-Blot, x * 83600, calculated
130000
-
polymerized LOXL1 precursor protein, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
homodimer, subunit interface structure, overview
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, X-ray structure determination and analysis at 1.65 A resolution, modelling
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
denatured by urea during purification and refolded by stepwise dialysis in the presence of N-lauroylsarcosinate and Cu2+
-
enzyme is resistant to high urea concentrations
remarkably stable in concentrated solutions of urea
-
sucrose, sorbitol, and mannitol are less effective in stabilization and preservation of the enzyme compared to trehalose
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, powdered tissue, full enzyme activity for at least 4 months
-
lyophilized purified recombinant LOX, loss of 73% activity without stabilizing agent, loss of 4% activity in presence of 10 mM trehalose
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
46.9fold from aorta by DEAE-cellulose ion exchange chromatography and gel filtration
-
affinity, gel-filtration, ion-exchange
-
affinity, ion-exchange
-
from aorta, to homogeneity, solubilization from connective tissue by 4-6 M urea
-
highly purified enzyme peptides
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immobilized metal chelate column chromatography
lysyl oxidase is a highly insoluble enzyme requiring high concentrations of urea to solubilize. Development and optimization of a method to obtain lysyl oxidase in high yields directly from an Escherichia coli culture without the need for refolding of inclusion bodies using nutrient rich media, overview
-
nickel affinity column chromatography and ultrafiltration
-
recombinant His-tagged mature enzyme and C-terminally deleted enzyme by nickel affinity chromatography
-
recombinant, N-terminally His6-tagged proteolytically processed forms of LOX, LOXL1, and LOXL2 from Escherichia coli inclusion bodies by nickel chelating affinity chromatography, to over 95% purity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning from cDNA library, DNA and amino acid sequence determination and analysis, expression of C-terminally His6-tagged LOX in Escherichia coli
-
expressed in CHO-K1 cells
-
expressed in Drosophila melanogaster Schneider-2 cells
expressed in Escherichia coli
expressed in immature dendritic cells derived from peripheral blod mononuclear cells
-
expressed in MEF cells
-
expressed in NCI-H1299, NIH-3T3 and PANC-1 cells
-
expressed in RFL6 cells
-
expressed in TREX 293 cells
-
expression analysis
-
expression in Escherichia coli
-
expression of mature enzyme and C-terminally deleted enzyme as N-terminally His6-tagged enzymes
-
expression of mature enzyme, proenzyme, and of isolated propeptide in Escherichia coli strain BL21-A1
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expression of proenzyme, mature enzyme, isolated propeptide, and mutant enzymes in HEK-293 cells as HA-tagged proteins
-
expression of proteolytically processed forms of LOX, LOXL1, and LOXL2 in Escherichia coli as N-terminally His6-tagged proteins
-
genes and isozymes LOXL1 and LOX, detailed expression analysis in aorta during growth and development, overview
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LOX genotyping of Asian non-areca nut chewers and arec nut chewers of different ages, overview
-
LOX propeptide is expressed in mouse mammary tumor virus Her-2/neu-driven breast cancer cell line
-
LOXL3 cDNA is expressed in human HT-1080 fibrosarcoma cells
real-time quantitative PCR enzyme expression analysis in wild-type and mutant mice
-
RT-PCR enzyme expression analysis in esophageal squamous cell carcinoma cells, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ability of torasemide to correct both lysyl oxidase overexpression and enhanced collagen cross-linking
-
enzyme expression is induced by TGFbeta treatment in smooth muscle cells
-
lineage-specific mutation of the type II TGFbeta receptor gene, Tgfbetar2, in both neural crest- and mesoderm-derived vascular smooth muscle precursors leads to absence of TGFbeta receptor function and reduced lysyl oxidase expression. The result is a poorly organized vascular elastic matrix in late-stage embryos, which is prone to dilation and aneurysm, due to a failure to initiate formation of the elastic matrix, rather than a failure to maintain a preexisting matrix, phenotype of Wnt1Cre/Tgfbr2 mutant embryos, overview
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LOX and LOXL2 are induced 13 and 7.5fold, respectively, by hypoxia-inducible transcription factor-1alpha and hypoxia-inducible transcription factor-2beta
-
LOX is induced by hypoxia, loss of Pdcd4 in human nonmetastatic breast cancer cells increases the expression of LOX mRNA, and loss of Pdcd4 also augments hypoxia induction of LOX
-
the enzyme expression is not influenced by diurnal variations, but significantly by the gender, female mice show lower enzyme mRNA expression than male ones
-
the enzyme is highly up-regulated in metastatic breast cancer cells and tissues
the enzyme is upregulated in polycystic ovarian tissue by LOX promoter binding of transcription factors, e.g. NF-kappaB and activator protein-1, induced in advanced glycation end product, AEG, signaling, overview
-
tumor suppressor Pdcd4 inhibits LOX expression, loss of Pdcd4 in human nonmetastatic breast cancer cells increases the expression of LOX mRNA
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G758T
-
the mutation is associated with the occurence of exfoliation syndrome
G794A
-
the mutation is associated with the occurence of exfoliation syndrome
N455Q
the mutant protein is not secreted into the medium since the mutation prevents N-glycosylation, so the proteins fail to fold properly and undergo rapid degradation
N644Q
the mutant protein is not secreted into the medium since the mutation prevents N-glycosylation, so the proteins fail to fold properly and undergo rapid degradation
R158Q
-
naturally occuring mutation, G to A polymorphism at nucleotide 473, causes oral submucous fibrosis and is associated to chewing of areca nuts, genotyping, overview
K314A
-
site-directed mutagenesis
Y349F
-
site-directed mutagenesis
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
convertion of recombinant, N-terminally His6-tagged proteolytically processed forms of LOX, LOXL1, and LOXL2 from Escherichia coli inclusion bodies to active enzymes by denaturation with 8 M urea prior to stepwise dialysis in presence of 2% N-laurylsarcosinate and 0.2 mM CuCl2
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
LOX can serve as a predictive marker of lymph node metastasis and prognosis in esophageal squamous cell carcinoma. Overall survival rates of the patients with esophageal squamous cell carcinoma with high LOX expression are significantly lower than those of the patients with esophageal squamous cell carcinoma with low LOX expression
medicine
synthesis
-
required for the normal biosynthesis and maturation of collagen and elastin