P28300 · LYOX_HUMAN
- ProteinProtein-lysine 6-oxidase
- GeneLOX
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids417 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:26838787).
Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (By similarity).
Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (By similarity).
Catalytic activity
- H2O + L-lysyl-[protein] + O2 = (S)-2-amino-6-oxohexanoyl-[protein] + H2O2 + NH4+
Cofactor
Protein has several cofactor binding sites:
Note: Contains 1 lysine tyrosylquinone.
Features
Showing features for site, binding site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein-lysine 6-oxidase
- EC number
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP28300
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Aortic aneurysm, familial thoracic 10 (AAT10)
- Note
- DescriptionA form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
- See alsoMIM:617168
Natural variants in AAT10
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_077534 | 79 | A>T | in AAT10; uncertain significance; dbSNP:rs752839330 | |
VAR_077535 | 154 | L>F | in AAT10; uncertain significance; dbSNP:rs767855588 | |
VAR_077536 | 248 | T>I | in AAT10; uncertain significance; 8% decrease of lysyl oxidase activity; dbSNP:rs1561420103 | |
VAR_077537 | 267 | Q>P | in AAT10; dbSNP:rs886040967 | |
VAR_077538 | 280 | S>I | in AAT10; 50% decrease of lysyl oxidase activity; dbSNP:rs886040965 | |
VAR_077539 | 298 | M>R | in AAT10; dbSNP:rs876657852 | |
VAR_077540 | 348 | S>R | in AAT10; 21% decrease of lysyl oxidase activity; dbSNP:rs1561417568 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_077534 | 79 | in AAT10; uncertain significance; dbSNP:rs752839330 | |||
Sequence: A → T | ||||||
Natural variant | VAR_077535 | 154 | in AAT10; uncertain significance; dbSNP:rs767855588 | |||
Sequence: L → F | ||||||
Natural variant | VAR_004282 | 158 | in dbSNP:rs1800449 | |||
Sequence: R → Q | ||||||
Mutagenesis | 183-184 | Abolishes sulfation and reduces binding to collagen; when associated with 186-F-F-187 and F-190. | ||||
Sequence: YY → FF | ||||||
Mutagenesis | 186-187 | Abolishes sulfation and reduces binding to collagen; when associated with 183-F-F-184 and F-190. | ||||
Sequence: YY → FF | ||||||
Mutagenesis | 190 | Abolishes sulfation and reduces binding to collagen; when associated with 183-F-F-184 and 186-F-F-187. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_077536 | 248 | in AAT10; uncertain significance; 8% decrease of lysyl oxidase activity; dbSNP:rs1561420103 | |||
Sequence: T → I | ||||||
Natural variant | VAR_077537 | 267 | in AAT10; dbSNP:rs886040967 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_077538 | 280 | in AAT10; 50% decrease of lysyl oxidase activity; dbSNP:rs886040965 | |||
Sequence: S → I | ||||||
Natural variant | VAR_077539 | 298 | in AAT10; dbSNP:rs876657852 | |||
Sequence: M → R | ||||||
Natural variant | VAR_077540 | 348 | in AAT10; 21% decrease of lysyl oxidase activity; dbSNP:rs1561417568 | |||
Sequence: S → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 528 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, propeptide, glycosylation, chain, modified residue, disulfide bond, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MRFAWTVLLLGPLQLCALVHC | ||||||
Propeptide | PRO_0000018520 | 22-168 | Removed by BMP1 | |||
Sequence: APPAAGQQQPPREPPAAPGAWRQQIQWENNGQVFSLLSLGSQYQPQRRRDPGAAVPGAANASAQQPRTPILLIRDNRTAAARTRTAGSSGVTAGRPRPTARHWFQAGYSTSRAREAGASRAENQTAPGEVPALSNLRPPSRVDGMVG | ||||||
Glycosylation | 81 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 97 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 144 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000018521 | 169-417 | Protein-lysine 6-oxidase, long form | |||
Sequence: DDPYNPYKYSDDNPYYNYYDTYERPRPGGRYRPGYGTGYFQYGLPDLVADPYYIQASTYVQKMSMYNLRCAAEENCLASTAYRADVRDYDHRVLLRFPQRVKNQGTSDFLPSRPRYSWEWHSCHQHYHSMDEFSHYDLLDANTQRRVAEGHKASFCLEDTSCDYGYHRRFACTAHTQGLSPGCYDTYGADIDCQWIDITDVKPGNYILKVSVNPSYLVPESDYTNNVVRCDIRYTGHHAYASGCTISPY | ||||||
Modified residue | 187 | Sulfotyrosine | ||||
Sequence: Y | ||||||
Chain | PRO_0000447885 | 219-417 | Protein-lysine 6-oxidase, short form | |||
Sequence: PYYIQASTYVQKMSMYNLRCAAEENCLASTAYRADVRDYDHRVLLRFPQRVKNQGTSDFLPSRPRYSWEWHSCHQHYHSMDEFSHYDLLDANTQRRVAEGHKASFCLEDTSCDYGYHRRFACTAHTQGLSPGCYDTYGADIDCQWIDITDVKPGNYILKVSVNPSYLVPESDYTNNVVRCDIRYTGHHAYASGCTISPY | ||||||
Disulfide bond | 238↔244 | |||||
Sequence: CAAEENC | ||||||
Disulfide bond | 291↔340 | |||||
Sequence: CHQHYHSMDEFSHYDLLDANTQRRVAEGHKASFCLEDTSCDYGYHRRFAC | ||||||
Cross-link | 320↔355 | Lysine tyrosylquinone (Lys-Tyr) | ||||
Sequence: KASFCLEDTSCDYGYHRRFACTAHTQGLSPGCYDTY | ||||||
Disulfide bond | 324↔330 | |||||
Sequence: CLEDTSC | ||||||
Disulfide bond | 351↔361 | |||||
Sequence: CYDTYGADIDC | ||||||
Modified residue | 355 | 2',4',5'-topaquinone | ||||
Sequence: Y | ||||||
Disulfide bond | 398↔412 | |||||
Sequence: CDIRYTGHHAYASGC |
Post-translational modification
The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.
Proteolytically cleaved by BMP1 which removes the propeptide (PubMed:31152061).
Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site (PubMed:31152061).
The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin (By similarity).
Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen (PubMed:31152061).
Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity (PubMed:31152061).
Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site (PubMed:31152061).
The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin (By similarity).
Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen (PubMed:31152061).
Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity (PubMed:31152061).
Sulfated at Tyr-187 and also at either Tyr-183 or Tyr-184 which enhances binding to collagen.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Heart, placenta, skeletal muscle, kidney, lung and pancreas.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with MFAP4 (PubMed:26601954).
Interacts (via propeptide) with EFEMP2; this interaction is strong and facilitates formation of ternary complexes with ELN during elastic fiber assembly; this interaction limits interaction of EFEMP2 with FBLN5 (PubMed:19855011).
Interacts (via propeptide) with EFEMP2; this interaction is strong and facilitates formation of ternary complexes with ELN during elastic fiber assembly; this interaction limits interaction of EFEMP2 with FBLN5 (PubMed:19855011).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P28300 | EFEMP2 O95967 | 7 | EBI-3893481, EBI-743414 | |
BINARY | P28300 | ELN P15502 | 2 | EBI-3893481, EBI-1222108 | |
BINARY | P28300 | FBLN5 Q9UBX5 | 2 | EBI-3893481, EBI-947897 | |
BINARY | P28300 | FBN1 P35555 | 2 | EBI-3893481, EBI-2505934 | |
BINARY | P28300 | PTPRK Q15262 | 4 | EBI-3893481, EBI-474052 | |
BINARY | PRO_0000018520 | DPT Q07507 | 2 | EBI-20724846, EBI-719535 | |
BINARY | PRO_0000018520 | EGF PRO_0000007541 P01133 | 2 | EBI-20724846, EBI-9076336 | |
BINARY | PRO_0000018520 | FN1 P02751 | 2 | EBI-20724846, EBI-1220319 | |
BINARY | PRO_0000018520 | FN1 PRO_0000390479 P02751 | 3 | EBI-20724846, EBI-15482592 | |
BINARY | PRO_0000018520 | PLG P00747 | 2 | EBI-20724846, EBI-999394 | |
BINARY | PRO_0000018520 | TGM2 P21980 | 3 | EBI-20724846, EBI-727668 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 64-89 | Disordered | ||||
Sequence: YQPQRRRDPGAAVPGAANASAQQPRT | ||||||
Region | 137-174 | Disordered | ||||
Sequence: AGASRAENQTAPGEVPALSNLRPPSRVDGMVGDDPYNP | ||||||
Region | 213-417 | Lysyl-oxidase like | ||||
Sequence: PDLVADPYYIQASTYVQKMSMYNLRCAAEENCLASTAYRADVRDYDHRVLLRFPQRVKNQGTSDFLPSRPRYSWEWHSCHQHYHSMDEFSHYDLLDANTQRRVAEGHKASFCLEDTSCDYGYHRRFACTAHTQGLSPGCYDTYGADIDCQWIDITDVKPGNYILKVSVNPSYLVPESDYTNNVVRCDIRYTGHHAYASGCTISPY |
Sequence similarities
Belongs to the lysyl oxidase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length417
- Mass (Da)46,944
- Last updated1993-10-01 v2
- Checksum6412A78443E03F04
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7P0SNB0 | A0A7P0SNB0_HUMAN | LOX | 232 | ||
H0YAL3 | H0YAL3_HUMAN | LOX | 61 | ||
B7ZAJ4 | B7ZAJ4_HUMAN | LOX | 187 | ||
B0AZT2 | B0AZT2_HUMAN | LOX | 120 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 30 | in Ref. 3 | ||||
Sequence: Q → H | ||||||
Sequence conflict | 31 | in Ref. 3 | ||||
Sequence: P → A | ||||||
Sequence conflict | 95 | in Ref. 3 | ||||
Sequence: R → A | ||||||
Sequence conflict | 102 | in Ref. 1; AAB21243 | ||||
Sequence: A → G | ||||||
Sequence conflict | 137 | in Ref. 2; AAA59525/AAB23549 | ||||
Sequence: A → R | ||||||
Sequence conflict | 139 | in Ref. 1; AAB21243 | ||||
Sequence: A → P | ||||||
Sequence conflict | 304-305 | in Ref. 1; AAB21243 | ||||
Sequence: YD → LY | ||||||
Sequence conflict | 315 | in Ref. 1; AAB21243 | ||||
Sequence: V → W |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S78694 EMBL· GenBank· DDBJ | AAB21243.1 EMBL· GenBank· DDBJ | mRNA | ||
M94054 EMBL· GenBank· DDBJ | AAA59525.1 EMBL· GenBank· DDBJ | mRNA | ||
S45875 EMBL· GenBank· DDBJ | AAB23549.1 EMBL· GenBank· DDBJ | mRNA | ||
AF039291 EMBL· GenBank· DDBJ | AAD02130.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312269 EMBL· GenBank· DDBJ | BAG35200.1 EMBL· GenBank· DDBJ | mRNA | ||
BC074820 EMBL· GenBank· DDBJ | AAH74820.1 EMBL· GenBank· DDBJ | mRNA | ||
BC074872 EMBL· GenBank· DDBJ | AAH74872.1 EMBL· GenBank· DDBJ | mRNA | ||
BC089436 EMBL· GenBank· DDBJ | AAH89436.1 EMBL· GenBank· DDBJ | mRNA | ||
L16895 EMBL· GenBank· DDBJ | AAA16870.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M84150 EMBL· GenBank· DDBJ | AAA59541.1 EMBL· GenBank· DDBJ | Genomic DNA |