LYOX_MOUSE
ID LYOX_MOUSE Reviewed; 411 AA.
AC P28301;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Protein-lysine 6-oxidase;
DE EC=1.4.3.13 {ECO:0000269|PubMed:27432961};
DE AltName: Full=Lysyl oxidase;
DE AltName: Full=Ras excision protein;
DE Contains:
DE RecName: Full=Protein-lysine 6-oxidase, long form {ECO:0000250|UniProtKB:P28300};
DE Contains:
DE RecName: Full=Protein-lysine 6-oxidase, short form {ECO:0000250|UniProtKB:P28300};
DE Flags: Precursor;
GN Name=Lox; Synonyms=Rrg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1678898; DOI=10.1126/science.1678898;
RA Kenyon K., Contente S., Trackman P.C., Tang J., Kagan H.M., Friedman R.M.;
RT "Lysyl oxidase and rrg messenger RNA.";
RL Science 253:802-802(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NIH Swiss;
RX PubMed=8100214; DOI=10.1006/geno.1993.1202;
RA Contente S., Csiszar K., Kenyon K., Friedman R.M.;
RT "Structure of the mouse lysyl oxidase gene.";
RL Genomics 16:395-400(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP ROLE OF PROPEPTIDE.
RX PubMed=16251195; DOI=10.1074/jbc.m506832200;
RA Thomassin L., Werneck C.C., Broekelmann T.J., Gleyzal C., Hornstra I.K.,
RA Mecham R.P., Sommer P.;
RT "The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for
RT deposition onto elastic fibers.";
RL J. Biol. Chem. 280:42848-42855(2005).
RN [5]
RP PROTEOLYTIC CLEAVAGE BY BMP1.
RX PubMed=20181949; DOI=10.1074/jbc.m109.088864;
RA Maruhashi T., Kii I., Saito M., Kudo A.;
RT "Interaction between periostin and BMP-1 promotes proteolytic activation of
RT lysyl oxidase.";
RL J. Biol. Chem. 285:13294-13303(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF MET-292.
RX PubMed=27432961; DOI=10.1073/pnas.1601442113;
RG Brigham Genomic Medicine;
RA Lee V.S., Halabi C.M., Hoffman E.P., Carmichael N., Leshchiner I.,
RA Lian C.G., Bierhals A.J., Vuzman D., Mecham R.P., Frank N.Y.,
RA Stitziel N.O.;
RT "Loss of function mutation in LOX causes thoracic aortic aneurysm and
RT dissection in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:8759-8764(2016).
CC -!- FUNCTION: Responsible for the post-translational oxidative deamination
CC of peptidyl lysine residues in precursors to fibrous collagen and
CC elastin. Regulator of Ras expression. May play a role in tumor
CC suppression. Plays a role in the aortic wall architecture
CC (PubMed:27432961). {ECO:0000269|PubMed:27432961}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-lysyl-[protein] + O2 = (S)-2-amino-6-oxohexanoyl-
CC [protein] + H2O2 + NH4(+); Xref=Rhea:RHEA:24544, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:12448, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:131803; EC=1.4.3.13;
CC Evidence={ECO:0000269|PubMed:27432961};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:P16636};
CC -!- COFACTOR:
CC Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489;
CC Evidence={ECO:0000250|UniProtKB:P33072};
CC Note=Contains 1 lysine tyrosylquinone. {ECO:0000250|UniProtKB:P33072};
CC -!- SUBUNIT: Interacts with MFAP4. {ECO:0000250|UniProtKB:P28300}.
CC -!- INTERACTION:
CC P28301; Q7TSK7: Adamtsl2; NbExp=3; IntAct=EBI-642911, EBI-25406979;
CC P28301; P17879: Hspa1b; NbExp=2; IntAct=EBI-642911, EBI-397360;
CC P28301; Q9H324: ADAMTS10; Xeno; NbExp=3; IntAct=EBI-642911, EBI-7096115;
CC P28301; Q6UY14: ADAMTSL4; Xeno; NbExp=2; IntAct=EBI-642911, EBI-742002;
CC P28301; P08107: HSPA1B; Xeno; NbExp=6; IntAct=EBI-642911, EBI-629985;
CC P28301; P04049: RAF1; Xeno; NbExp=2; IntAct=EBI-642911, EBI-365996;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27432961}. Secreted,
CC extracellular space.
CC -!- TISSUE SPECIFICITY: Expressed in aorta (at protein level). Expressed in
CC embryonic, juvenil and adult aorta. {ECO:0000269|PubMed:27432961}.
CC -!- PTM: The lysine tyrosylquinone cross-link (LTQ) is generated by
CC condensation of the epsilon-amino group of a lysine with a topaquinone
CC produced by oxidation of tyrosine. {ECO:0000250|UniProtKB:P33072}.
CC -!- PTM: Proteolytically cleaved by BMP1 which removes the propeptide
CC (PubMed:20181949). Also proteolytically cleaved by ADAMTS2 and
CC ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream
CC of the BMP1 cleavage site (By similarity). The propeptide plays a role
CC in directing the deposition of this enzyme to elastic fibers, via
CC interaction with tropoelastin (PubMed:16251195). Cleavage by BMP1 to
CC remove the propeptide does not increase enzymatic activity but
CC increases binding to collagen (By similarity). Cleavage by ADAMTS2
CC produces a form with reduced collagen-binding activity (By similarity).
CC {ECO:0000250|UniProtKB:P28300, ECO:0000269|PubMed:16251195,
CC ECO:0000269|PubMed:20181949}.
CC -!- PTM: Sulfated at Tyr-181 and also at either Tyr-177 or Tyr-178 which
CC enhances binding to collagen. {ECO:0000250|UniProtKB:P28300}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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DR EMBL; M65142; AAA19032.1; -; mRNA.
DR EMBL; M65143; AAA20185.1; -; mRNA.
DR EMBL; L04262; AAA99899.1; -; Genomic_DNA.
DR EMBL; L04263; AAA99899.1; JOINED; Genomic_DNA.
DR EMBL; L04264; AAA99899.1; JOINED; Genomic_DNA.
DR EMBL; BC018439; AAH18439.1; -; mRNA.
DR CCDS; CCDS50289.1; -.
DR PIR; A47005; OXMSL.
DR RefSeq; NP_001273110.1; NM_001286181.1.
DR RefSeq; NP_001273111.1; NM_001286182.1.
DR RefSeq; NP_034858.2; NM_010728.3.
DR AlphaFoldDB; P28301; -.
DR SMR; P28301; -.
DR BioGRID; 201191; 7.
DR IntAct; P28301; 16.
DR MINT; P28301; -.
DR STRING; 10090.ENSMUSP00000129247; -.
DR BindingDB; P28301; -.
DR ChEMBL; CHEMBL4523209; -.
DR GlyGen; P28301; 2 sites.
DR iPTMnet; P28301; -.
DR PhosphoSitePlus; P28301; -.
DR PaxDb; P28301; -.
DR PeptideAtlas; P28301; -.
DR PRIDE; P28301; -.
DR ProteomicsDB; 292150; -.
DR Antibodypedia; 25606; 855 antibodies from 35 providers.
DR DNASU; 16948; -.
DR Ensembl; ENSMUST00000025409; ENSMUSP00000025409; ENSMUSG00000024529.
DR Ensembl; ENSMUST00000171470; ENSMUSP00000129247; ENSMUSG00000024529.
DR GeneID; 16948; -.
DR KEGG; mmu:16948; -.
DR UCSC; uc008exe.2; mouse.
DR CTD; 4015; -.
DR MGI; MGI:96817; Lox.
DR VEuPathDB; HostDB:ENSMUSG00000024529; -.
DR eggNOG; ENOG502QWQR; Eukaryota.
DR GeneTree; ENSGT00940000154779; -.
DR HOGENOM; CLU_002555_2_1_1; -.
DR InParanoid; P28301; -.
DR OMA; GCHMSTY; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; P28301; -.
DR TreeFam; TF326061; -.
DR Reactome; R-MMU-1566948; Elastic fibre formation.
DR Reactome; R-MMU-2243919; Crosslinking of collagen fibrils.
DR BioGRID-ORCS; 16948; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Lox; mouse.
DR PRO; PR:P28301; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P28301; protein.
DR Bgee; ENSMUSG00000024529; Expressed in stroma of bone marrow and 177 other tissues.
DR ExpressionAtlas; P28301; baseline and differential.
DR Genevisible; P28301; MM.
DR GO; GO:0005581; C:collagen trimer; IDA:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; IDA:UniProtKB.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0035905; P:ascending aorta development; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0060326; P:cell chemotaxis; IMP:MGI.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0030199; P:collagen fibril organization; IMP:MGI.
DR GO; GO:0061448; P:connective tissue development; IGI:MGI.
DR GO; GO:0035906; P:descending aorta development; IMP:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; IMP:MGI.
DR GO; GO:0048251; P:elastic fiber assembly; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:MGI.
DR GO; GO:0055001; P:muscle cell development; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR GO; GO:0018057; P:peptidyl-lysine oxidation; ISS:UniProtKB.
DR GO; GO:0035791; P:platelet-derived growth factor receptor-beta signaling pathway; IMP:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:MGI.
DR GO; GO:0018158; P:protein oxidation; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:1903010; P:regulation of bone development; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; IMP:MGI.
DR GO; GO:2000586; P:regulation of platelet-derived growth factor receptor-beta signaling pathway; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:1900120; P:regulation of receptor binding; IMP:MGI.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; IMP:MGI.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR GO; GO:0009725; P:response to hormone; ISO:MGI.
DR GO; GO:0048545; P:response to steroid hormone; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; ISO:MGI.
DR InterPro; IPR001695; Lysyl_oxidase.
DR InterPro; IPR019828; Lysyl_oxidase_CS.
DR Pfam; PF01186; Lysyl_oxidase; 1.
DR PRINTS; PR00074; LYSYLOXIDASE.
DR PROSITE; PS00926; LYSYL_OXIDASE; 1.
PE 1: Evidence at protein level;
KW Copper; Disulfide bond; Glycoprotein; LTQ; Metal-binding; Oxidoreductase;
KW Reference proteome; Secreted; Signal; Sulfation; TPQ.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT PROPEP 22..162
FT /note="Removed by BMP1"
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT /id="PRO_0000018522"
FT CHAIN 163..411
FT /note="Protein-lysine 6-oxidase, long form"
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT /id="PRO_0000018523"
FT CHAIN 213..411
FT /note="Protein-lysine 6-oxidase, short form"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT /id="PRO_0000447886"
FT REGION 58..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..411
FT /note="Lysyl-oxidase like"
FT BINDING 286
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 288
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 290
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT SITE 212..213
FT /note="Cleavage; by ADAMTS2 and ADAMTS14"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT MOD_RES 181
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT MOD_RES 349
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 232..238
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 285..334
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 318..324
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 345..355
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 392..406
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CROSSLNK 314..349
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT MUTAGEN 292
FT /note="M->R: Homozygous mice display tortuous vessels
FT aneurysm, loss of oxidase activity and die perinatally of
FT aortic aneurysm and dissection. Heterozygous mice display
FT thicker arterial wall with discontinuous elastic lamellae."
FT /evidence="ECO:0000269|PubMed:27432961"
FT CONFLICT 333
FT /note="A -> G (in Ref. 2; AAA99899)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 411 AA; 46701 MW; DBC0563A9C0AEB52 CRC64;
MRFAWAVLLL GPLQLCPLLR CAPQTPREPP AAPGAWRQTI QWENNGQVFS LLSLGAQYQP
QRRRDPSATA RRPDGDAASQ PRTPILLLRD NRTASTRART PSPSGVAAGR PRPAARHWFQ
AGFSPSGARD GASRRAANRT ASPQPPQLSN LRPPSHIDRM VGDDPYNPYK YSDDNPYYNY
YDTYERPRPG SRNRPGYGTG YFQYGLPDLV PDPYYIQAST YVQKMSMYNL RCAAEENCLA
SSAYRADVRD YDHRVLLRFP QRVKNQGTSD FLPSRPRYSW EWHSCHQHYH SMDEFSHYDL
LDANTQRRVA EGHKASFCLE DTSCDYGYHR RFACTAHTQG LSPGCYDTYA ADIDCQWIDI
TDVQPGNYIL KVSVNPSYLV PESDYTNNVV RCDIRYTGHH AYASGCTISP Y
