LYOX_RAT
ID LYOX_RAT Reviewed; 411 AA.
AC P16636;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Protein-lysine 6-oxidase {ECO:0000305};
DE EC=1.4.3.13 {ECO:0000305|PubMed:16432278};
DE AltName: Full=Lysyl oxidase;
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 {ECO:0000312|RGD:3015};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Aorta;
RX PubMed=1973052; DOI=10.1021/bi00472a016;
RA Trackman P.C., Pratt A.M., Wolanski A., Tang S.-S., Offner G.D.,
RA Troxler R.F., Kagan H.M.;
RT "Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted
RT amino acid sequence.";
RL Biochemistry 29:4863-4870(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RX PubMed=1678281; DOI=10.1021/bi00247a025;
RA Trackman P.C., Pratt A.M., Wolanski A., Tang S.-S., Offner G.D.,
RA Troxler R.F., Kagan H.M.;
RT "Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted
RT amino acid sequence.";
RL Biochemistry 30:8282-8282(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 PROTEIN SEQUENCE OF 163-167, AND PROTEOLYTIC PROCESSING OF N-TERMINUS.
RX PubMed=8636146; DOI=10.1074/jbc.271.12.7113;
RA Panchenko M.V., Stetler-Stevenson W.G., Trubetskoy O.V., Gacheru S.N.,
RA Kagan H.M.;
RT "Metalloproteinase activity secreted by fibrogenic cells in the processing
RT of prolysyl oxidase. Potential role of procollagen C-proteinase.";
RL J. Biol. Chem. 271:7113-7119(1996).
RN [5]
RP FUNCTION, AND COFACTOR.
RX PubMed=16432278; DOI=10.1093/toxsci/kfj112;
RA Zhao Y., Gao S., Chou I.N., Toselli P., Stone P., Li W.;
RT "Inhibition of the expression of lysyl oxidase and its substrates in
RT cadmium-resistant rat fetal lung fibroblasts.";
RL Toxicol. Sci. 90:478-489(2006).
RN [6]
RP PROTEOLYTIC PROCESSING OF N-TERMINUS.
RX PubMed=1349020; DOI=10.1016/s0021-9258(18)42494-5;
RA Trackman P.C., Bedell-Hogan D., Tang J., Kagan H.M.;
RT "Post-translational glycosylation and proteolytic processing of a lysyl
RT oxidase precursor.";
RL J. Biol. Chem. 267:8666-8671(1992).
RN [7]
RP CLEAVAGE OF SIGNAL PEPTIDE AFTER CYS-21, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=26479776; DOI=10.1021/acs.jproteome.5b00820;
RA Tsuchiya T., Osaki T., Minamino N., Sasaki K.;
RT "Peptidomics for studying limited proteolysis.";
RL J. Proteome Res. 14:4921-4931(2015).
CC -!- FUNCTION: Responsible for the post-translational oxidative deamination
CC of peptidyl lysine residues in precursors to fibrous collagen and
CC elastin (PubMed:16432278). Regulator of Ras expression. May play a role
CC in tumor suppression. Plays a role in the aortic wall architecture (By
CC similarity). {ECO:0000250|UniProtKB:P28301,
CC ECO:0000269|PubMed:16432278}.
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:0000305|PubMed:16432278};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000269|PubMed:16432278};
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};
CC -!- SUBUNIT: Interacts with MFAP4. Interacts (via propeptide) with EFEMP2;
CC this interaction is strong and facilitates formation of ternary
CC complexes with ELN during elastic fiber assembly; this interaction
CC limits interaction of EFEMP2 with FBLN5.
CC {ECO:0000250|UniProtKB:P28300}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P28301}.
CC Secreted, extracellular space.
CC -!- TISSUE SPECIFICITY: Aorta and lung. {ECO:0000269|PubMed:1973052}.
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 (By
CC similarity). Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but
CC not by ADAMTS3, at an additional cleavage site downstream of the BMP1
CC cleavage site (By similarity). The propeptide plays a role in directing
CC the deposition of this enzyme to elastic fibers, via interaction with
CC tropoelastin (By similarity). Cleavage by BMP1 to remove the propeptide
CC does not increase enzymatic activity but increases binding to collagen
CC (By similarity). Cleavage by ADAMTS2 produces a form with reduced
CC collagen-binding activity (By similarity).
CC {ECO:0000250|UniProtKB:P28300, ECO:0000250|UniProtKB:P28301}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U11038; AAC52176.1; -; mRNA.
DR EMBL; J02903; AAA41537.1; -; mRNA.
DR EMBL; BC078861; AAH78861.1; -; mRNA.
DR PIR; B40557; OXRTL.
DR RefSeq; NP_058757.1; NM_017061.2.
DR RefSeq; XP_006254775.1; XM_006254713.3.
DR RefSeq; XP_006254776.1; XM_006254714.3.
DR AlphaFoldDB; P16636; -.
DR SMR; P16636; -.
DR IntAct; P16636; 2.
DR STRING; 10116.ENSRNOP00000065314; -.
DR GlyGen; P16636; 2 sites.
DR PhosphoSitePlus; P16636; -.
DR PaxDb; P16636; -.
DR PRIDE; P16636; -.
DR Ensembl; ENSRNOT00000019844; ENSRNOP00000019844; ENSRNOG00000014426.
DR GeneID; 24914; -.
DR KEGG; rno:24914; -.
DR UCSC; RGD:3015; rat.
DR CTD; 4015; -.
DR RGD; 3015; Lox.
DR eggNOG; ENOG502QWQR; Eukaryota.
DR GeneTree; ENSGT00940000154779; -.
DR HOGENOM; CLU_002555_2_1_1; -.
DR InParanoid; P16636; -.
DR OMA; GCHMSTY; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; P16636; -.
DR TreeFam; TF326061; -.
DR BRENDA; 1.4.3.13; 5301.
DR BRENDA; 3.4.24.14; 5301.
DR Reactome; R-RNO-1566948; Elastic fibre formation.
DR Reactome; R-RNO-2243919; Crosslinking of collagen fibrils.
DR PRO; PR:P16636; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000014426; Expressed in lung and 19 other tissues.
DR Genevisible; P16636; RN.
DR GO; GO:0005581; C:collagen trimer; ISO:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IMP:RGD.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; IDA:RGD.
DR GO; GO:0035904; P:aorta development; ISO:RGD.
DR GO; GO:0035905; P:ascending aorta development; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0060326; P:cell chemotaxis; IMP:MGI.
DR GO; GO:1990869; P:cellular response to chemokine; ISO:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0030199; P:collagen fibril organization; IDA:RGD.
DR GO; GO:0061448; P:connective tissue development; ISO:RGD.
DR GO; GO:0035906; P:descending aorta development; ISO:RGD.
DR GO; GO:0071897; P:DNA biosynthetic process; ISO:RGD.
DR GO; GO:0048251; P:elastic fiber assembly; IMP:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0055001; P:muscle cell development; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0018158; P:protein oxidation; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:1903010; P:regulation of bone development; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; ISO:RGD.
DR GO; GO:2000586; P:regulation of platelet-derived growth factor receptor-beta signaling pathway; ISO:RGD.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:1900120; P:regulation of receptor binding; IMP:MGI.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISO:RGD.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0042060; P:wound healing; IMP:RGD.
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; Direct protein sequencing; Disulfide bond; Glycoprotein; LTQ;
KW Metal-binding; Oxidoreductase; Reference proteome; Secreted; Signal;
KW Sulfation; TPQ.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:26479776"
FT PROPEP 22..162
FT /note="Removed by BMP1"
FT /evidence="ECO:0000269|PubMed:8636146"
FT /id="PRO_0000018524"
FT CHAIN 163..411
FT /note="Protein-lysine 6-oxidase, long form"
FT /evidence="ECO:0000269|PubMed:8636146"
FT /id="PRO_0000018525"
FT CHAIN 213..411
FT /note="Protein-lysine 6-oxidase, short form"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT /id="PRO_0000447888"
FT REGION 60..168
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"
SQ SEQUENCE 411 AA; 46559 MW; EE68C9C5AACDFC1A CRC64;
MRFAWTVLFL GQLQFCPLLR CAPQAPREPP AAPGAWRQTI QWENNGQVFS LLSLGAQYQP
QRRRDSSATA PRADGNAAAQ PRTPILLLRD NRTASARART PSPSGVAAGR PRPAARHWFQ
VGFSPSGAGD GASRRAANRT ASPQPPQLSN LRPPSHVDRM VGDDPYNPYK YSDDNPYYNY
YDTYERPRSG SRHRPGYGTG YFQYGLPDLV PDPYYIQAST YVQKMSMYNL RCAAEENCLA
SSAYRADVRD YDHRVLLRFP QRVKNQGTSD FLPSRPRYSW EWHSCHQHYH SMDEFSHYDL
LDASTQRRVA EGHKASFCLE DTSCDYGYHR RFACTAHTQG LSPGCYDTYA ADIDCQWIDI
TDVQPGNYIL KVSVNPSYLV PESDYSNNVV RCEIRYTGHH AYASGCTISP Y
